Drug Delivery Devices And Related Systems And Methods

ABSTRACT

This disclosure relates to drug delivery devices and related systems and methods. In some aspects, a drug delivery device includes a drug vial holder and a mechanism configured to compress a drug vial between upper and lower members of the drug vial holder.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application Ser.No. 61/222,146, filed on Jul. 1, 2009, which is incorporated byreference herein.

TECHNICAL FIELD

This invention relates to drug delivery devices and related systems andmethods.

BACKGROUND

As soon as kidney failure is diagnosed, patients are typically givenmedication to help control the symptoms and slow the progress of thedamage to the kidneys. Patients with chronic kidney failure generallytake drugs to control the balance of minerals in the body and prevent areduction of red blood cells (anemia).

Healthy kidneys produce the hormone erythropoietin (often shortened to“EPO”), which stimulates the production of red blood cells in the bonemarrow. Red blood cells play a key role in the delivery of oxygen totissues in the body. If the body does not have enough EPO, it can leadto anemia. This often causes a drop in physical and mental performanceand an increased risk for cardio-vascular diseases. To prevent anemia,chronic renal patients normally receive a synthetic version oferythropoietin (also referred to as “EPO”) that, like the naturalerythropoietin, stimulates the production of red blood cells.

Anemia can be managed using a variety of different drugs. For example,since iron is also needed to produce red blood cells, many dialysispatients also take iron preparations. Venofer® (iron sucrose injection,USP) is indicated in the treatment of iron deficiency anemia in patientsundergoing chronic hemodialysis who are receiving supplemental EPOtherapy.

SUMMARY

In one aspect of the invention, a drug delivery device includes a drugvial holder including an upper member and a lower member. The upper andlower members are configured to receive a drug vial therebetween. Thedrug delivery device also includes a mechanism configured to move atleast one of the upper and lower members relative to the other of theupper and lower members such that, when a drug vial is disposed betweenthe upper and lower members and the at least one of the upper and lowermembers is moved toward the other, the drug vial is compressed betweenthe upper and lower members.

In another aspect of the invention, a drug delivery system includes adrug delivery device including a drug vial holder having an upper memberand a lower member, and a mechanism connected to the drug vial holder.The drug delivery system also includes a drug vial disposed between theupper and lower members of the drug vial holder. The mechanism isconfigured to move at least one of the upper and lower members relativeto the other of the upper and lower members in a manner to compress thedrug vial therebetween.

In an additional aspect of the invention, a dialysis system includes adialysis machine that includes a blood pump. The system further includesa drug delivery device that includes a drug pump, a drug vial holderincluding an upper member and a lower member, and a mechanism configuredto move at least one of the upper and lower members relative to theother of the upper and lower members such that, when a drug vial isdisposed between the upper and lower members and the at least one of theupper and lower members is moved toward the other, the drug vial iscompressed between the upper and lower members. The system also includesa blood line set including a blood line that is operably connected tothe blood pump and a fluid line set including a fluid line that isoperably connected to the drug pump and is connected to a spike. Thefluid line set is configured such that the spike can be placed in fluidcommunication with the drug vial retained between the upper and lowermembers of the drug vial holder by moving the drug vial holder and thedrug vial relative to the spike. The fluid line is in fluidcommunication with the blood line set such that a drug can be deliveredfrom the drug vial to the blood line set when the drug pump is operated.

In a further aspect of the invention, a drug vial spiking deviceincludes a cup-shaped member having a base and a sidewall that at leastpartially form a recess configured to receive at least a portion of adrug vial, a spike extending from a central region of the base, andmultiple springs extending from the base of the cup-shaped member intothe recess. The spike defines a channel extending therethrough, and thesprings are configured to apply a force to a drug vial in a directionaway from the base of the cup-shaped member when at least a portion ofthe drug vial is positioned in the recess.

In another aspect of the invention, a fluid line set includes multiplefluid lines and multiple drug vial spiking devices, each of which isconnected to one of the fluid lines. Each of the drug vial spikingdevices includes a cup-shaped member having a base and a sidewall thatat least partially form a recess configured to receive at least aportion of a drug vial, a spike extending from a central region of thebase, and multiple springs extending from the base of the cup-shapedmember into the recess. The spike defines a channel extendingtherethrough, and the springs are configured to apply a force to a drugvial in a direction away from the base of the cup-shaped member when atleast a portion of the drug vial is positioned in the recess.

In an additional aspect of the invention, a fluid line set includes aframe having a top member, a manifold, and at least one connectingmember that extends between and is attached to the top member and themanifold. The manifold defines a fluid passage extending therethrough.The fluid line set also includes multiple spikes that extend from thetop member and multiple fluid lines connected to the top member and themanifold. Each of the spikes defines a fluid channel. Each of the fluidlines is in fluid communication with the channel of one of the spikesand with the fluid passage extending through the manifold. The frame isconfigured to hold the fluid lines in a spaced apart configuration.

In a further aspect of the invention, a drug delivery system includes adrug delivery device having a surface from which multiple pumps extendand a fluid line set. The fluid line set includes a frame having a topmember, a manifold, and at least one connecting member that extendsbetween and is attached to the top member and the manifold. The manifolddefines a fluid passage extending therethrough. The fluid line set alsoincludes multiple spikes that extend from the top member and multiplefluid lines connected to the top member and the manifold. Each of thespikes defines a fluid channel. Each of the fluid lines is in fluidcommunication with the channel of one of the spikes and with the fluidpassage extending through the manifold. The frame is configured to holdthe fluid lines in a spaced apart configuration, and the fluid line setis configured to be secured to the drug delivery device in a manner suchthat each of the fluid lines is operably connected to one of the pumps.

In yet another aspect of the invention, a dialysis system includes adialysis machine including a blood pump and a blood line set including ablood line that is operably connected to the blood pump. The systemfurther includes a drug delivery device having a surface from whichmultiple drug pumps extend and a fluid line set. The fluid line setincludes a frame having a top member, a manifold, and at least oneconnecting member that extends between and is attached to the top memberand the manifold. The manifold defines a fluid passage extendingtherethrough. The fluid line set also includes multiple spikes thatextend from the top member and multiple fluid lines connected to the topmember and the manifold. Each of the spikes defines a fluid channel.Each of the fluid lines is in fluid communication with the channel ofone of the spikes and with the fluid passage extending through themanifold. The frame is configured to hold the fluid lines in a spacedapart configuration. The fluid line set is configured to be secured tothe drug delivery device in a manner such that each of the fluid linesis operably connected to one of the pumps. The fluid line set is furtherconfigured to be placed in fluid communication with the blood line setsuch that, when one of the spikes of the fluid line set is disposedwithin a drug vial and the drug pump operably connected to the fluidline that is in fluid communication with the channel of that spike isoperated, a drug is delivered from the drug vial to the blood line setvia the fluid line set.

In a further aspect of the invention, a drug vial spiking assemblyincludes a drug vial spike device including a spike extending from abase and a cover secured to the drug vial spike device. The spike has atip opposite the base, and the cover is movable toward the base from afirst position in which the cover at least partially covers the tip ofthe spike to a second position in which the tip of the spike is fullyexposed.

In an additional aspect of the invention, a fluid line set includesmultiple fluid lines, multiple drug vial spike devices, and multiplecovers. Each of the drug vial spike devices is connected to one of thefluid lines and includes a spike extending from a base. The spike ofeach drug vial spike device has a tip opposite the base. Each of thecovers is secured to one the drug vial spike devices and is movabletoward the base from a first position in which the cover at leastpartially covers the tip of the spike of the spike device to which thecover is secured to a second position in which the tip of the spike ofthe spike device to which the cover is secured is fully exposed.

In another aspect of the invention, a drug delivery device includes apump extending from a surface of the drug delivery device and a doorhaving an inner surface and including a spring-loaded member exposedalong the inner surface. The spring-loaded member defines a recessconfigured to receive a portion of the pump when the door is closed.When a fluid line is positioned in the recess and the door is closed,the fluid line is compressed between the spring-loaded member and thepump in a manner such that the fluid line is occluded in at least onelocation.

In a further aspect of the invention, a drug delivery system includesmultiple fluid lines and multiple occluders. Each occluder is operablyconnected to one of the fluid lines. The system also includes a singlepump operably connected to a drug delivery line that is in fluidcommunication with each of the fluid lines. The drug delivery system isconfigured to operate the occluders and the pump in a manner such that,when the fluid lines are placed in fluid communication with multipledrug vials, drugs are drawn from the multiple drug vials into the drugdelivery line.

In a further aspect of the invention, a dialysis system includes adialysis machine including a blood pump, a modular drug delivery deviceincluding at least one drug pump and a plurality of drug vial holders,and a housing to which the blood pump and the modular drug deliverydevice are secured. A blood line set including multiple blood lines anda vented chamber in fluid communication with the multiple blood lines isconnected to the blood pump in a manner such that, when the blood lineset is connected to a patient and the blood pump is operated, blood ofthe patient is passed through the blood line set. A drug line setincluding multiple drug lines is connected to the vented chamber of theblood line set and to the at least one drug pump in a manner such that,when the drug line set is fluidly connected to one or more drug vialscontained in the multiple drug vial holders and the at least one drugpump is operated, drug is delivered from the one or more drug vials tothe vented chamber of the blood line set via the drug line set. Thedialysis system also includes a control unit configured to operate theblood pump and the drug pump to simultaneously delivery drug and bloodto the vented chamber.

In an additional aspect of the invention, a method includes inserting aspike through a seal of a drug vial to allow fluid communication betweenan interior of the drug vial and a channel defined by the spike, anddeforming a portion of the seal away from a body of the drug vial tofacilitate removal of drug from the interior of the drug vial. Deformingthe portion of the seal away from the body of the drug vial is carriedout by using a mechanism to move the spike relative to the drug vial.

In yet another aspect of the invention, a method includes compressing aseal of a drug vial between a cap of the drug vial and a neck portion orbody portion of the drug vial by disposing the drug vial between anupper member and a lower member of a drug vial holder and moving atleast one of the upper and lower members of the drug vial holder towardthe other of the upper and lower members of the drug vial holder. Whilemaintaining the seal in a compressed state, a spike is inserted throughthe seal of the drug vial to allow fluid communication between aninterior of the drug vial and a channel defined by the spike.

In a further aspect of the invention, a drug delivery method includespassing a first drug through a drug delivery line to a vented chamber,passing a gas bubble through the drug delivery line to the ventedchamber, and then passing a second drug through the drug delivery lineto the vented chamber. The gas bubble extends across substantially anentire inner diameter of the drug delivery line as the gas bubble passestherethrough.

In another aspect of the invention, a drug delivery method includesdetermining that a first drug contained in a first container connectedto a drug delivery line and a second drug contained in a secondcontainer connected to the drug delivery line are not suitable formixing together prior to being delivered to a patient, and afterdetermining that the first and second drugs are not suitable for mixing,operating a drug delivery device in a manner to deliver the first drugthrough the drug delivery line and to a patient, deliver a gas bubblethrough the drug delivery line; and then deliver the second drug throughthe drug delivery line and to a patient.

In an additional aspect of the invention, a method includes selecting adrug vial combination by comparing a prescribed drug dosage to a dosingschedule. The dosing schedule provides multiple drug vial combinationsassociated with multiple drug dosages. The selected drug vialcombination includes one or more drug vials, and each of the one or moredrug vials contains a first drug. The method further includes deliveringsubstantially all of the first drug from each of the one or more drugvials to a patient by operating a pump of a drug delivery device towhich the one or more drug vials are connected.

In a further aspect of the invention, a method includes receiving by oneor more computers data related to a prescribed drug dosage, anddetermining by the one or more computers one or more recommended drugvial combinations by comparing the prescribed dosage to a dosingschedule. Each of the one or more recommended drug vial combinationsincludes one or more drug vials, and the one or more drug vials of eachof the one or more recommended drug vial combinations contain an amountof drug substantially equal to the prescribed dosage. The dosingschedule includes data representing a plurality of drug vialcombinations associated with a plurality of drug dosages.

In another aspect of the invention, a computer program product resideson a computer readable medium, and the computer program product includesinstructions for causing a processor to determine one or morerecommended drug vial combinations by comparing a prescribed dosage to adosing schedule. Each of the one or more recommended drug vialcombinations includes one or more drug vials, and the one or more drugvials of each of the one or more recommended drug vial combinationscontain an amount of drug substantially equal to the prescribed dosage.The dosing schedule includes data representing multiple different drugvial combinations associated with multiple different drug dosages.

In another aspect of the invention, a method includes fully evacuatingand delivering a drug from its vial to a patient in an automatedfashion.

In an additional aspect of the invention, a drug delivery device isconfigured to fully evacuate a drug from its vial and deliver the drugto a patient in an automated fashion.

In a further aspect of the invention, a method includes developing orcalculating a dosing schedule that provides guidance to the prescriberand/or administrator regarding the correct average dose to beadministered using permutations of multiple vials of a drug pertreatment, and/or over multiple treatments.

In another aspect of the invention, a device is configured to calculatea dosing schedule that provides guidance to the prescriber and/oradministrator regarding the correct average dose to be administeredusing permutations of multiple vials of a drug per treatment, and/orover multiple treatments.

In an additional aspect of the invention, a method includesautomatically delivering several different drugs in succession using onepumping device, and without allowing the drugs to mix prior to deliveryto the patient.

In a further aspect of the invention, a drug delivery device isconfigured to automatically deliver several different drugs insuccession using one pumping device, and without allowing the drugs tomix prior to delivery to the patient.

Implementations can include one or more of the following features.

In certain implementations, the mechanism is configured to compress aseal disposed between a cap of the drug vial and a neck portion of thedrug vial when the drug vial is disposed between the upper and lowermembers and the at least one of the upper and lower members is movedtoward the other.

In some implementations, multiple projections extend from a surface ofthe lower member. The projections are configured to dent adjacentportions of a cap of the drug vial into a seal of the drug vial when thedrug vial is compressed between the upper and lower members.

In certain implementations, the projections are configured to pierce theadjacent portions of the cap of the drug vial when the drug vial iscompressed between the upper and lower members.

In some implementations, the lower member defines an opening sized toreceive a drug vial spike, and the opening is arranged to align with aseal of the drug vial when the drug vial is disposed between the upperand lower members.

In certain implementations, the lower member defines a recess configuredto receive a portion of the drug vial therein.

In some implementations, the mechanism is configured to move the uppermember, the lower member, and the drug vial disposed therebetween inunison after compressing the drug vial between the upper and lowermembers.

In certain implementations, the mechanism includes a motor that, whenoperated, causes the at least one of the upper and lower members to movetoward the other.

In some implementations, the mechanism is configured in a manner suchthat, after operating the motor for a period of time to compress thedrug vial between the upper and lower members, continued operation ofthe motor causes the upper and lower members to move in unison.

In certain implementations, the mechanism is configured to move theupper member of the drug vial holder toward the lower member of the drugvial holder.

In some implementations, the mechanism includes a rotatable, threadeddrive shaft to which a threaded drive member is secured, and the drivemember is configured such that rotation of the drive shaft causes thedrive member to move axially along the drive shaft.

In certain implementations, the drive member includes a ball screw.

In some implementations, the drive member is secured to the upper memberof the vial holder in a manner such that axial movement of the drivemember causes axial movement of the upper member.

In certain implementations, the drive member is secured to a cross barthat is attached to at least one extension member, and the at least oneextension member is attached to the upper member of the drug vialholder.

In some implementations, the mechanism includes at least one resilientmember configured to resist downward movement of the lower member of thedrug vial holder.

In certain implementations, the at least one resilient member includes aspring.

In some implementations, the at least one resilient member is configuredto provide sufficient resistance to downward movement of the lowermember to cause a seal of a drug vial disposed between the upper andlower members to be compressed when the at least one of the upper andlower members is moved toward the other.

In certain implementations, the at least one resilient member isconfigured to collapse and allow the drug vial to move in unison withthe upper and lower members after the seal of the drug vial has beencompressed.

In some implementations, the drug delivery device further includes atleast one spike disposed beneath the drug vial holder, and the mechanismis configured to move the upper and lower members of the drug vialholder in unison relative to the spike to cause the spike to penetrate adrug vial disposed between the upper and lower members.

In certain implementations, the drug delivery device further includes apump configured to be operably connected to a fluid line that is influid communication with a drug vial disposed between the upper andlower members of the drug vial holder such that operation of the pumpcan draw drug from the drug vial and through the fluid line.

In some implementations, the mechanism is manually operable.

In certain implementations, the springs are leaf springs.

In some implementations, at least one of the leaf springs includes aprojection extending from a surface thereof, and the projection isarranged to contact a cap of the drug vial when the drug vial isinserted into the recess.

In certain implementations, the projection and the at least one leafspring are configured in a manner such that the projection dents a capof the drug vial when the drug vial is inserted into the recess.

In some implementations, the base defines multiple openings configuredto receive the multiple springs when the drug vial is fully insertedinto the recess.

In certain implementations, at least one of the springs includes aprojection extending therefrom, and the at least one of the springs andthe projection are configured such that the projection dents a cap ofthe drug vial when the drug vial is inserted into the recess withsufficient force to cause the cap of the vial to contact the base of thecup-shaped member.

In some implementations, the drug vial spiking device further includesat least one bi-stable member attached to the base, and the bi-stablemember is positioned above an aperture defined in the base.

In certain implementations, the bi-stable member is configured to bestably positioned in a first position and a second position, and atleast a portion of the bi-stable member is visible to a user when thebi-stable member is in the second position.

In some implementations, the bi-stable member in the second positionindicates that a drug vial has been fully inserted into the recess.

In certain implementations, the portion of the member visible to theuser protrudes from an outer surface of the base.

In some implementations, the bi-stable member includes a projectionextending from its upper surface.

In certain implementations, the projection is configured to push thebi-stable member from the first position to the second position when thedrug vial is fully inserted into the recess such that the vial contactsthe base of the cup-shaped member.

In some implementations, the spike includes a portion configured toengage an inner surface of a seal of a drug vial after the spike isinserted into the drug vial.

In certain implementations, the portion of the spike extends laterallyin at least one direction to a greater extent than a remainder of thespike.

In some implementations, the portion of the spike is substantiallyconical.

In certain implementations, the portion of the spike includes a barb.

In some implementations, the spike defines multiple openings along anouter surface of the spike, and each of the openings is in fluidcommunication with the channel.

In certain implementations, a portion of the sidewall forms a flangethat retains the portion of the vial within the recess.

In some implementations, the flange is configured to contact a cap ofthe vial.

In certain implementations, the frame includes two connecting membersthat extend between and are attached to the top member and the manifold.

In some implementations, the frame is rectangular.

In certain implementations, the frame further includes a cross bar thatextends between and is connected to the two connecting members.

In some implementations, the cross bar defines multiple spaced apartrecesses, and each of the recesses is configured to retain one of thefluid lines.

In certain implementations, a projection extends from a surface of theframe, and the projection is configured to mate with a matching hole ina drug delivery device.

In some implementations, the projection is configured to engage thematching hole in the drug delivery device in a manner to releasablysecure the fluid line set to the drug delivery device.

In certain implementations, the projection and the matching hole arehexagonal.

In some implementations, each of the top member, the manifold, and theat least one connecting member has a greater rigidity than the fluidlines.

In certain implementations, the fluid line set further includes a coverdisposed over at least one of the spikes.

In some implementations, the drug delivery device includes a door, andthe door and the surface of the drug delivery device form a cassettecompartment configured to receive the frame and the fluid lines of thefluid line set therein when the door is closed.

In certain implementations, an inner surface of the door defines arecessed region configured to receive the frame of the fluid line set.

In some implementations, an inner surface of the door defines a holeconfigured to receive a projection that extends from a surface of thesupport frame.

In certain implementations, the hole and the projection are configuredto engage one another in a manner to releasably secure the fluid lineset to the door of the drug delivery device.

In some implementations, the pumps are peristaltic pumps.

In certain implementations, the drug delivery device further includesmultiple air bubble detectors positioned on the surface, and the fluidline set is configured to be disposed adjacent the surface of thedialysis machine in a manner such that each fluid line is aligned withone of the air bubble detectors.

In some implementations, the drug delivery device further includes adrug vial holder that is movable in a manner such that, when a drug vialis disposed in the drug vial holder, the drug vial can be moved withrespect to the fluid line set to cause one of the spikes of the fluidline set to penetrate the vial.

In certain implementations, the cover is resilient such that when aforce applied to the cover to move the cover from the first position tothe second position is removed, the cover returns to approximately thefirst position.

In some implementations, a length of the cover is greater than a lengthof the spike when the cover is in the first position, and the length ofthe cover is less than the length of the spike when the cover is in thesecond position.

In certain implementations, the cover includes an upper member, a lowermember, and at least one elongate structure connecting the upper memberto the lower member.

In some implementations, each of the upper and lower members defines anaperture configured to receive the spike therein.

In certain implementations, the at least one elongate structure includesmultiple circumferentially spaced, resilient columns.

In some implementations, each of the resilient columns defines a channelalong its peripheral surface that facilitates collapse of the columnwhen a force is applied to the column along a longitudinal axis of thecolumn.

In certain implementations, the at least one elongate structure includesa foam tube.

In some implementations, the elongate structure includes a spring.

In certain implementations, the spring is a coil spring that at leastpartially surrounds the spike.

In some implementations, the member is an inflated member.

In certain implementations, the inflated member is an inflated balloon.

In some implementations, the inflated member at least partiallysurrounds the spike.

In certain implementations, the inflated member and the spike areconfigured such that the spike punctures the inflated member when aforce is applied to the inflated member in a direction along the spike.

In some implementations, the cover is a coil spring that at leastpartially surrounds the spike.

In certain implementations, the cover includes an elongate tubularmember that fits over the spike.

In some implementations, the drug vial spiking assembly further includesa structure that is fixed relative to the spike and is configured tocontact the elongate tubular member and resist further movement of theelongate tubular member when the elongate tubular member has been movedto the second position.

In certain implementations, multiple projections extend from a surfaceof the cover, and the projections are configured to dent adjacentportions of a cap of a drug vial into a rubber seal of the drug vialwhen the drug vial is pressed against the cover with sufficient force tocause the cover to move from the first position to the second position.

In some implementations, the pump is configured to pump fluid throughthe fluid line when the pump is operated, the fluid line is positionedin the recess, the door is closed, and the pump is operated.

In certain implementations, a first spring is connected to a first endregion of the spring-loaded member, and a second spring is connected toa second end region of the spring loaded member, and the first andsecond springs are each secured to a structure of the door.

In some implementations, the pump is rigidly fixed to a housing of thedrug delivery device.

In certain implementations, the pump is a peristaltic pump comprising aframe and multiple rollers positioned about a circumference of theframe.

In some implementations, the frame is rotatably secured to a rod that isfixed to a housing of the drug delivery device.

In certain implementations, the drug delivery device further includes adrive mechanism configured to operate the peristaltic pump.

In some implementations, the drive mechanism includes a motor having anoutput shaft and a worm gear attached to the output shaft, and the wormgear is engaged with a gear secured to the frame such that rotation ofthe output shaft causes the frame of the peristaltic pump to rotate.

In certain implementations, the drug delivery device includes multiplepumps extending from the surface of the drug delivery device, the doorincludes multiple spring-loaded members exposed along the inner surface,and each of the spring-loaded members defines a recess configured toreceive a portion of one of the pumps when the door is closed.

In some implementations, the inner surface of the door defines arecessed region configured to receive a frame of a fluid line settherein.

In certain implementations, the inner surface of the door furtherdefines multiple recessed channels configured to receive fluid lines ofthe fluid line set therein.

In some implementations, the drug delivery device further includesmultiple air bubble detectors, and each of the air bubble detectors isarranged to substantially align with a fluid line when fluid lines arepositioned within the recesses of the door and the door is closed suchthat the air bubble detectors can detect air within the fluid lines.

In certain implementations, the drug delivery device further includesmultiple drug vial holders positioned above the multiple pumps, and eachof the drug vial holders is configured to retain at least one drug vial.

In some implementations, the drug delivery device is configured tooperate the pumps in a manner such that, when fluid lines are positionedin the recesses of the door, the door is closed, and each of the fluidlines is in fluid communication with a drug vial retained by one of thedrug vial holders, an air bubble is passed through a drug delivery lineconnected to each of the fluid lines between the delivery of drug fromconsecutive vials.

In certain implementations, the drug delivery device is configured tooperate the pumps in a manner to pass an air bubble through the drugdelivery line after completion of the delivery of drug from each vial.

In some implementations, the drug delivery device is part of a dialysismachine.

In certain implementations, the fluid line is connected to a bloodcircuit of the dialysis machine in a manner such that fluid is deliveredthrough the fluid line to the blood circuit when the pump is operated.

In some implementations, the drug delivery system is configured tooperate the occluders and the pump in a manner such that drug is onlydrawn into the drug delivery line from one of the drug vials at a time.

In certain implementations, the drug delivery system further includesmultiple air bubble detectors, and each of the air bubble detectors issubstantially aligned with one of the fluid lines such that the airbubble detectors can detect air within the fluid lines.

In some implementations, the drug delivery system is configured tooperate the occluders and the pump in a manner such that, when themultiple fluid lines are placed in fluid communication with multipledrug vials, an air bubble is passed through the drug delivery linebetween the delivery of drug from consecutive vials.

In certain implementations, the drug delivery system is configured tooperate the occluders and the pump in a manner to pass an air bubblethrough the drug delivery line after completion of the delivery of drugfrom each vial.

In some implementations, the drug delivery system is part of a dialysismachine.

In certain implementations, the drug delivery line is connected to ablood circuit of the dialysis machine in a manner such that fluid can bedelivered through the drug delivery line to the blood circuit when thepump is operated.

In some implementations, the seal is a rubber seal.

In certain implementations, deforming the portion of the seal includesusing the spike to apply a force to the portion of the seal.

In some implementations, the force is a frictional force.

In certain implementations, moving the spike relative to the vialincludes applying a force to the body of the drug vial in a directionopposite the force applied to the portion of the seal.

In some implementations, the method further includes maintaining theseal in a compressed state while inserting the spike through the seal.

the seal is compressed between a cap of the drug vial and a neck portionof the drug vial.

In certain implementations, the seal is compressed between a cap of thedrug vial and a body portion of the drug vial.

In some implementations, the mechanism includes a spring.

In certain implementations, the mechanism is an automated mechanism.

In some implementations, the seal is compressed between a cap of thedrug vial and a neck portion of the drug vial.

In certain implementations, the seal is a rubber seal.

In some implementations, the method further includes denting portions ofthe cap into the seal.

In certain implementations, denting the portions of the cap into theseal includes forcing the cap against projections extending from asurface of the lower member of the drug vial holder.

In some implementations, denting the portions of the cap into the sealincludes piercing portions of the cap.

In certain implementations, the method further includes deforming aportion of the seal away from a body of the drug vial to facilitateremoval of drug from the drug vial.

In some implementations, deforming the portion of the seal includesusing the spike to apply a force to the portion of the seal.

In certain implementations, the force is a frictional force.

In some implementations, the method of claim further includes applying aforce to the body portion of the drug vial in a direction opposite theforce applied to the portion of the seal.

In certain implementations, the method further includes applying a forceto the neck portion of the drug vial in a direction opposite the forceapplied to the portion of the seal.

In some implementations, the first and second drugs are the same drug.

In certain implementations, the first and second drugs are differentdrugs.

In some implementations, the first and second drugs are not suitable formixing together prior to being delivered to a patient.

In certain implementations, the first drug is synthetic erythropoietinand the second drug is iron sucrose.

In some implementations, the gas bubble pushes some of the first drugthrough the drug delivery line to the vented chamber as the gas bubbleis passed through the drug delivery line to the vented chamber.

In certain implementations, the gas bubble pushes substantially allresidual first drug in the drug delivery line to the vented chamber asthe gas bubble is passed through the drug delivery line to the ventedchamber.

In some implementations, passing the first drug through the drugdelivery line includes operating a first pump that is operably connectedto a first fluid line to move the first drug into the drug delivery linefrom the first fluid line, and passing the second drug through the drugdelivery line includes operating a second pump that is operablyconnected to a second fluid line to move the second drug into the drugdelivery line from the second fluid line.

In certain implementations, passing the gas bubble through the drugdelivery line includes operating the first pump to move the gas bubbleinto the drug delivery line from the first fluid line.

In some implementations, passing the first drug, the gas bubble, and thesecond drug through the drug delivery line includes operating a singlepump that is operably connected to the drug delivery line.

In certain implementations, the first drug is drawn into the drugdelivery line from a first fluid line, and the second drug is drawn intothe drug delivery line from a second fluid line.

In some implementations, the drug delivery method further includesoccluding the second fluid line while the first drug is being drawn intothe drug delivery line, and occluding the first fluid line while thesecond drug is being drawn into the drug delivery line.

In certain implementations, the gas bubble is drawn into the drugdelivery line from the first fluid line.

In some implementations, the first drug is moved into the drug deliveryline from a first drug container that is connected to the drug deliveryline via a first fluid line, and the second drug is moved into the drugdelivery line from a second drug container that is connected to the drugdelivery line via a second fluid line.

In certain implementations, passing the gas bubble through the drugdelivery line includes moving gas into the drug delivery line from thefirst drug container.

In some implementations, the drug delivery method further includesdetecting gas in the first fluid line and occluding a region of thefirst fluid line when a desired volume of gas has passed beyond theregion of the fluid line.

In certain implementations, the drug delivery method further includesallowing the gas bubble to escape to atmosphere via a vent of the ventedchamber.

In some implementations, the drug deliver method further includesintroducing blood into the vented chamber.

In certain implementations, the drug delivery method further includesallowing the first drug to mix with the blood in the vented chamber, andthen delivering the resulting mixture of the first drug and the blood toa patient.

In some implementations, the gas bubble is an air bubble.

In certain implementations, the drug delivery method further includespassing a third drug through the drug delivery line to the ventedchamber.

In some implementations, the drug delivery method further includespassing a gas bubble through the drug delivery line after passing thesecond drug through the drug delivery line and before passing the thirddrug through the drug delivery line.

In certain implementations, the drug delivery method further includesventing the gas bubble to atmosphere before the second drug is deliveredto the patient such that the gas bubble is not delivered to the patient.

In some implementations, a control unit of the drug delivery deviceselects the drug vial combination.

In certain implementations, the control unit runs a computer programthat automatically selects the drug vial combination based on theprescribed dosage and operator preferences.

In some implementations, the prescribed dosage and operator preferencesare entered into the drug delivery device by the operator.

In certain implementations, the prescribed dosage is electronicallytransmitted to the control unit from a database storing data comprisingthe prescribed dosage.

In some implementations, the prescribed dosage is entered into thedatabase by or at the direction of a physician of the patient.

In certain implementations, the control unit controls operation of thepump.

In some implementations, the drug vial combinations and associated drugdosages of the dosing schedule are based on a single treatment.

In certain implementations, the drug vial combinations and associateddrug dosages of the dosing schedule are based on multiple treatments.

In some implementations, the drug vial combination is selected based atleast in part on the number of drug vials required over the course oneor more treatments.

In certain implementations, the drug vial combination is selected basedat least in part on the number of drug vials required over the course ofmultiple treatments.

In some implementations, the drug vial combination is selected based inpart on a drug dosage consistency that would be provided by the drugvial combination over the course of multiple treatments.

In certain implementations, the method further includes displaying theone or more recommended drug vial combinations on a display.

In some implementations, determining the one or more recommended drugvial combinations includes determining the one or more drug vialcombinations from the dosing schedule that utilize the fewest drug vialsover the course of one or more treatments and that contain an amount ofdrug substantially equal to the prescribed drug dosage.

In certain implementations, determining the one or more recommended drugvial combinations further includes determining the one or more drug vialcombinations from the dosing schedule that utilize the fewest drug vialsover the course of multiple treatments and that contain an amount ofdrug substantially equal to the prescribed drug dosage.

In some implementations, determining the one or more recommended drugvial combinations includes determining one or more drug vialcombinations from the dosing schedule that result in a drug dosageconsistency within an acceptable consistency range over the course ofone or more treatments and that contain an amount of drug substantiallyequal to the prescribed drug dosage.

In certain implementations, determining the one or more recommended drugvial combinations further includes determining the one of the one ormore drug vial combinations that utilizes the fewest number of drugvials over the course of the one or more treatments and that contains anamount of drug substantially equal to the prescribed drug dosage.

In some implementations, determining the one or more recommended drugvial combinations includes determining one or more drug vialcombinations from the dosing schedule that result in a drug dosageconsistency within an acceptable consistency range over the course ofmultiple treatments and that contain an amount of drug substantiallyequal to the prescribed drug dosage.

In certain implementations, determining the one or more recommended drugvial combinations further includes determining the one of the one ormore drug vial combinations from the dosing schedule that utilizes thefewest number of drug vials over the course of the multiple treatmentsand that contains an amount of drug substantially equal to theprescribed drug dosage.

In some implementations, determining the one or more recommended drugvial combinations includes determining the drug vial combination fromthe dosing schedule that provides the greatest drug dosage consistencyover the course of the one or more treatments and that contains anamount of drug substantially equal to the prescribed drug dosage.

In certain implementations, determining the one or more recommended drugvial combinations includes determining the drug vial combination thatprovides the greatest drug dosage consistency over the course ofmultiple treatments and that contains an amount of drug substantiallyequal to the prescribed drug dosage.

In some implementations, the data is transmitted from a user interfaceof a medical system.

In certain implementations, the medical system is a hemodialysis system.

In some implementations, the one or more computers is a processor.

Implementations can include one or more of the following advantages.

In some implementations, drug delivery systems and methods permit thedrug to be fully evacuated from the vial. Fully evacuating the drug fromthe vial helps to ensure that substantially all of the drug is deliveredto the patient. This reduces the amount of drug that is unused andwasted relative to many conventional drug delivery techniques. Inaddition, ensuring that substantially all of the drug is removed fromthe vial increases the accuracy with which drug prescribed drug dosagesare delivered to the patients.

In certain implementations, the drug delivery systems and methods allowthe seal (e.g., rubber seal or stopper) of the vial to be compressedbetween the body or neck portion and the cap of the vial to reduce(e.g., prevent) movement of the seal relative to the body or neckportion and the cap of the vial. Limiting the movement of the sealrelative to the body and cap of the vial can help to ensure that theseal does not bulge inwardly into the vial as the spike penetrates theseal. This can help to ensure that the drug is fully evacuated from thevial.

In some implementations, the spike is retracted slightly relative to thevial (e.g., by moving the vial away from the spike, by moving the spikeaway from the vial, or both) after the spike has penetrated the seal.Retracting the spike relative to the vial can cause the portion of theseal surrounding the spike to be deformed outwardly away from the vial,which can help to ensure that the drug is fully evacuated from the vial.

In certain implementations, the drug delivery system includes amechanism that, during operation, compresses the seal of the vialbetween the body and cap of the vial and then causes the spike topenetrate the seal. As explained above, compressing the seal helps toensure that the seal does not bulge inwardly into the vial as the spikepenetrates the seal. Providing a single mechanism that can both compressthe seal and cause the spike to penetrate the seal can increase thespeed and efficiency of the set up and delivery processes associatedwith the drug delivery system.

In some implementations, the fluid lines connected to the various spikesare retained by a structure (e.g., a frame) that holds the fluid linesin a spaced apart configuration. This arrangement can make it easier forthe user to load the fluid lines onto corresponding instruments of thedrug delivery device, such as air bubble detectors, occluders, and/orpumps.

In certain implementations the spikes are provided with one or morecovers that cover the spikes before they are inserted into the vials.This can help to prevent contamination of the spikes due to inadvertentcontact with the spikes prior to their insertion into the vials. Incertain implementations, the covers are configured to automaticallyexpand over the spikes when the spikes are removed from the vials. Thiscan help to prevent the operator from pricking himself or herself withthe spikes when removing the spikes from the vials and disposing of thespikes.

In some implementations, the drug delivery systems and methods permitmultiple different drugs or other therapeutic agents to be delivered insuccession without substantial mixing of the drugs or therapeuticagents. By delivering several different drugs or therapeutic agents insuccession to the patient without allowing the drugs or therapeuticagents to mix prior to delivery to the patient, adverse patientreactions resulting from the mixing of incompatible drugs or therapeuticagents prior to delivery can be avoided.

In certain implementations, the user is provided with a dosing scheduleof the proper combination of vials per treatment, which also helps toreduce (e.g., minimize) the amount of drug that is wasted. Single usedrug vials can be used for only one patient and then must generally bediscarded. If the combination of vials selected for a treatment containa greater amount of drug than is prescribed for the particular patientbeing treated, then some of the drug will not be administered to thepatient and must be discarded. The dosing schedule can prevent this fromhappening by informing the user of all combinations of vials that can beused based on the patient's prescription without wasting any of thedrug.

In addition, the dosing schedule can inform the user of the vialcombinations that result in the fewest number of vials used pertreatment, per week, and/or per month. This allows the user to selectvial combinations that reduce (e.g., minimize) the number of vials usedand thus reduce (e.g., minimize) the number of vials and the amount ofcorresponding packaging materials that must be discarded over a givenperiod of time.

The dosing schedule can also inform the user of the dosage consistencythat the patient receives throughout a treatment or throughout multipletreatments with different vial combinations. This allows the user toselect a vial combination that provides a desired dosage consistency.

Other aspects, features, and advantages will be apparent from thedescription and drawings, and from the claims.

DESCRIPTION OF DRAWINGS

FIG. 1 is a schematic of a hemodialysis machine that includes a modulardrug delivery device. A drug administration fluid line set and multipledrug vials are secured to the modular drug delivery device.

FIG. 2 is a perspective view of the modular drug delivery device of thehemodialysis machine of FIG. 1 and the drug administration fluid lineset and drug vials that are secured to the modular drug delivery device.

FIG. 3 is an exploded view of a drug vial, a drug vial spike, and afluid line. The fluid line and drug vial spike are components of thedrug administration fluid line set that is used with the modular drugdelivery device of the hemodialysis machine of FIG. 1 to deliver a drugfrom the drug vial to a blood circuit of the hemodialysis machine.

FIGS. 4 and 5 are perspective and top views, respectively, of the drugvial spike shown in FIG. 3.

FIG. 6 is a cross-sectional view of the drug vial spike of FIG. 5, takenalong line 6-6 in FIG. 5.

FIG. 7 is a schematic of certain components of the modular drug deliverydevice of the hemodialysis machine of FIG. 1 in use with the drug vialsand the drug administration fluid line set secured thereto. The drugadministration fluid line set includes a series of fluid lines and adrug vial spike connected to each of the drug vials.

FIG. 8 illustrates a portion of a user interface of the modular drugdelivery device during various different stages of the drug delivery.

FIG. 9 illustrates a snapshot of the user interface of the modular drugdelivery device during the drug delivery.

FIG. 10 is a cross-sectional view of a drug vial spike including acentral spike with a conical tip.

FIG. 11 is a cross-sectional view of a drug vial spike including acentral spike with a barb.

FIG. 12 is a perspective view a portion of the drug administration fluidline set illustrated in FIG. 1 with a spike cover disposed over thespikes of the drug administration fluid line set.

FIG. 13 is a perspective view of a drug administration fluid line setthat includes a frame that holds fluid lines of the drug administrationfluid line set in a spaced configuration.

FIG. 14 is a front view of a hemodialysis system that includes ahemodialysis machine with a different type modular drug delivery deviceintegrated therein. A drug administration fluid line cassette and drugvials are secured between a door and inner face of the modular drugdelivery device.

FIG. 15 is a perspective, exploded view of the drug administration fluidline cassette that is partially illustrated in FIG. 14 and a spike coverthat is disposed over spikes of the drug administration fluid linecassette prior to use.

FIG. 16 is a perspective view of the hemodialysis machine of FIG. 14with the door of the drug delivery device opened and the drugadministration fluid line cassette and vials removed to expose variouscomponents of the drug delivery device.

FIG. 17 is a perspective view of certain components of the drug deliverydevice of FIG. 14, including peristaltic pumps and their drivemechanisms.

FIG. 18 is a perspective view of drive mechanisms that are used tooperate drug vial holders of the drug delivery device of FIG. 14.

FIG. 19 is a perspective view of another type of drive mechanism thatcan be used to drive the drug vial holders of the drug delivery deviceof FIG. 14.

FIG. 20 is a side view of an additional type of drive mechanism that canbe used to operate the drug vial holders of the drug delivery device ofFIG. 14.

FIG. 21 is a perspective view of drug vial holders each of whichincludes pointed projections extending from its lower member for dentingthe caps of drug vials held by the drug vial holder assembly during use.

FIG. 22 is a perspective view of a drug vial including a cap that hasbeen dented by one of the drug vial holders of FIG. 21 to help fix arubber seal of the vial relative to the cap and body of the vial.

FIG. 23 is a schematic side view of a manually operated drive mechanismand an associated drug vial holder that can be operated by the manuallyoperated drive mechanism.

FIGS. 24-29 are front views of various different types of spike coverssecured to drug vial spikes.

FIG. 30 is a schematic of a stand alone drug delivery system.

FIG. 31 illustrates a portion of a hemodialysis machine that includes amodular drug delivery device that is configured for use with a singledrug vial.

FIGS. 32 and 33 are perspective views of the modular drug deliverydevice of the hemodialysis machine of FIG. 31.

FIG. 34 is an exploded view of the modular drug delivery device of thehemodialysis machine of FIG. 31.

FIG. 35 illustrates a vented drug vial spike.

FIG. 36 is a schematic of the vented drug vial spike of FIG. 35connected to a drug vial and a pressure transducer.

FIG. 37 is a schematic view of the vented drug vial spike of FIG. 35connected to a drug vial and a pressure reservoir, which is connected toa pressure transducer.

DETAILED DESCRIPTION

Referring to FIG. 1, a hemodialysis system 100 includes a hemodialysismachine 101 that has a drug delivery system 102. The drug deliverysystem 102 includes a modular drug delivery device 103 and a disposabledrug administration fluid line set 107 that is connected to the drugdelivery device 103. A drug delivery line 104 of the drug administrationfluid line set 107 is fluidly connected to a blood circuit of thehemodialysis system 100. The blood circuit of the hemodialysis system100 includes, among other things, a series of blood lines 105, a dripchamber 106, and a dialyzer 110. A blood pump (e.g., a peristaltic pump)108 is configured to pump blood through the blood circuit duringtreatment. The hemodialysis system 100 also includes a dialysate circuitand various other components that, for the sake of simplicity, are notdescribed in detail. During hemodialysis treatment, blood is drawn fromthe patient and, after passing through the drip chamber 106, is pumpedthrough the dialyzer 110 where toxins are removed from the blood andcollected in dialysate passing through the dialyzer. The cleansed bloodis then returned to the patient, and the dialysate including the toxins(referred to as “spent dialysate”) is disposed of or recycled andreused. As discussed in greater detail below, during the hemodialysistreatment, drugs (e.g., Epogen® and Venofer®) are also delivered to thedrip chamber 106 using the drug delivery system 102. The drugs mix withthe patient's blood within the drip chamber 106 and are then deliveredto the patient along with the patient's blood.

As shown in FIG. 2, the modular drug delivery device 103 includes a drugvial holder 112 that defines four channels 114. Each of the channels 114is designed to hold captive a drug vial 116, 118. The channels 114 can,for example, be recesses that are formed within the drug vial holder 112and that are sized and shaped to receive only the caps and narrow neckportions of the vials 116, 118 such that the larger body portions of thevials sit above the holder 112. In the illustrated implementation, thevial 116 furthest to the left contains Venofer® and the three vials 118to the right of the Venofer® vial 116 contain Epogen®. Venofer® (ironsucrose injection, USP) is a sterile, aqueous complex of polynucleariron (III)-hydroxide in sucrose that is manufactured by American Regent,Inc. Venofer® is indicated in the treatment of iron deficiency anemia inpatients undergoing chronic hemodialysis who are receiving supplementalerythropoietin therapy. Epogen® is a drug that stimulates the productionof red blood cells and is also commonly used in dialysis patients.Epogen® is manufactured by Amgen, Inc.

The disposable drug administration fluid line set 107 is fluidlyconnected to each of the vials 116, 118. The drug administration fluidline set 107 includes four drug vial spikes 120 that connect to thevials 116, 118 in a manner to allow the drugs within the vials (i.e.,the Venofer® and Epogen®) to flow into feeder lines 122 via the drugvial spikes 120. Each of the feeder lines 122 is attached to aT-connector 124. The T-connectors 124 and associated tubing segments 126connect the feeder lines 124 to the drug delivery line 104. The drugvial spikes 120 can be formed of one or more relatively rigid medicalgrade plastics, such as polycarbonate or alphamethylstyrene (AMS), andthe various fluid lines can be formed of a more flexible medical gradeplastic, such as polyvinylchloride (PVC).

Each of the feeder lines 122, as shown in FIG. 2, passes through (e.g.,is threaded through) a bubble detector 128. The bubble detectors 128 arecapable of detecting air bubbles within the feeder lines 122. As aresult, each of the bubble detectors 128 can determine whether itsassociated drug vial 116, 118 is empty during treatment, because air isdrawn from the vial 116, 118 into the feeder line 122 when the vial isempty. In some implementations, the bubble detectors 122 are opticaldetectors. The OPB 350 bubble detector made by Optek can, for example,be used. Other types of optical detectors can alternatively oradditionally be used. Similarly, other types of sensors, such as sensorsutilizing ultrasound technology can be used as the bubble detectors.Examples of such sensors include the AD8/AD9 Integral UltrasonicAir-In-Line, Air Bubble Detector and the BD8/BD9 Integral Ultrasonic AirBubble, Air-In-Line & Liquid Level Detection Sensors (manufactured byIntrotek International (Edgewood, N.Y.)). In some implementations, thebubble detector 128 includes a sensor that, in addition to sensing thepresence of an air bubble within its associated feeder line 122, cansense the presence of the feeder line itself.

Downstream of the bubble detectors 128, the feeder lines 122 passthrough (e.g., are threaded through) occluders 130. Each of theoccluders 130 can be used to crimp the portion of the feeder line 122disposed therein to prevent fluid from passing through the feeder line122. In some implementations, the occluders 130 are solenoid based rams.Alternatively or additionally, other types of automated occluders can beused. The occluders 130 can be collectively operated in a manner suchthat only one feeder line 122 is unclamped at any particular time.

The drug delivery line 104 to which each of the feeder lines 122 isfluidly connected passes through (e.g., is threaded through) aperistaltic drug pump 132. The drug pump 132 includes multiple rollersthat compress the drug delivery line 104 in a manner to create a“pillow” of fluid (i.e., a “pillow” of air or liquid) that is pinchedbetween two points of the drug delivery line 104 that are compressed bythe pump rollers. The rollers are arranged around a circumference of arotatable frame. As the frame is rotated, the rollers force the “pillow”of fluid through the drug delivery line 104 toward the drip chamber 106(shown in FIG. 1). When the pump 132 is being operated and one of theoccluders 130 is open (i.e., not clamping its associated feeder line122), vacuum pressure is applied to the drug vial 116, 118 that isconnected to the feeder line 122 associated with the open occluder 130.In certain cases, the initial pressure in the drug vial 116, 118 isequal to the ambient pressure and when all of the drug has beendelivered, the ending pressure within the vial is about −10 psi. Inother words, the pressure within the drug vial 116, 118 progresses fromambient to −10 psi as the drug is delivered. The pump 132 is configuredto generate a vacuum pressure within the drug delivery line 104 andfeeder line 122 that exceeds the competing vacuum within the drug vial116, 118. As a result, the drug is drawn from the vial 116, 118, throughthe drug vial spike 120, through the feeder line 122, and into the drugdelivery line 104.

In some implementations, each channel 114 of the drug vial holder 112includes a sensor to sense the presence of a vial or drug container. Incertain implementations, each drug channel 114 includes a system whichidentifies the drug vial installed. The drug vial identification systemcan, for example, include a bar code reader that reads bar codes on thevials. Different types of sensors can alternatively or additionally beused. In some implementations, for example, the vial identificationsystem uses RFID technology. Other examples of suitable sensors includecolor sensors for sensing the color of color coded drug vials and/or forsensing the color of the drug within the vial, photo sensors (e.g.,cameras) that are equipped with text recognition software to read texton the drug vial, capacitive sensors that permit different size vials tobe detected, load cells or scales that detect the mass of the vial, andconductivity or electrical impedance sensors that can be used todetermine the type of drug within the vial.

The drug delivery device 103 also includes a control unit (e.g., amicroprocessor) that can power the various components of the drugdelivery device 103. The control unit can receive signals from and sendsignals to the various components of the drug delivery device 103,including, but not limited to, the bubble detectors 128, the occluders130, the drug pump 132, the drug vial ID sensors, and other sensorsalong the drug lines. The control unit can control the variouscomponents of the drug delivery device 103 based on information receivedfrom these components. For example, the control unit can control theoccluders 130 to ensure that only one of the occluders 130 is open at atime. This helps to ensure that drug is pulled from only one of thevials 116, 118 at a time during treatment. The control unit can alsodetermine the volume of drug delivered based on operation data of thedrug pump 132 and can control the occluders 130 based on the drug volumedetermined to have been delivered. For example, upon determining thatthe prescribed volume of the drug has been delivered, the control unitcan close the occluder 130 associated with that drug vial 116, 118 andopen the occluder 130 associated with the next drug to be delivered.

The control unit can also control the timing with which the variousoccluders 130 are opened and closed. For example, after the fullcontents of a vial have been evacuated, air will be sucked into thefeeder line 122 associated with that vial. As the air passes through thefeeder line 122, the bubble detector 128 will detect the air andtransmit a signal to the control unit indicating that the vial is empty.In response, the control unit can close the occluder 130 associated withthe empty vial and open the occluder 130 associated with the vialcontaining the next drug to be delivered. Upon receiving informationfrom the bubble detectors 128 indicating that all of the vials have beenemptied, the control unit can turn off the drug pump 132.

The control unit can also control certain components of the drugdelivery device 103 based on signals received from the drug vial IDsensors, which indicate the presence of a vial and/or the identity ofthe vial contents. Such an arrangement can help to ensure that thecorrect vials (e.g., the correct number of vials and the vialscontaining the correct contents) are used for the treatment. Uponreceiving signals from the drug vial ID sensors that do not match theinputted treatment information, for example, an alarm (e.g., an audibleand/or visual alarm) can be activated. Alternatively or additionally,the drug delivery device 103 can be configured so that treatment cannotbe initiated until the sensors detect the correct combination of vials.

The drug delivery device 103 (e.g., the control unit of the drugdelivery device 103) is configured to sense if the blood pump 108 of thedialysis machine 101 is running and to pause drug delivery if the bloodpump 108 is stopped. This technique prevents ‘pooling’ of the delivereddrug in the drip chamber 106 during treatment.

Still referring to FIG. 2, the drug delivery device 103 further includesa user interface 134 that is connected to the control unit. The userinterface 134 includes right/left arrow keys that allow the user tonavigate through displays associated with the vials 116, 118. The userinterface 134 also includes up/down arrow keys that enable the user toset the desired dosage for each of the vials 116, 118. In addition, theuser interface 134 includes start and stop keys that allow the user tostart and stop the drug delivery device 103.

Any of various other types of user interfaces can alternatively oradditionally be used. In some implementations, the drug delivery deviceincludes a user interface that allows the user to select a drug toinfuse from a menu. In certain implementations, the user may confirmthat the drug identified by the drug vial ID sensor is correct and/ormake appropriate adjustments. The user interface can be used to inputand/or monitor various different treatment parameters. Examples of suchparameters include drug dosage, drug delivery rate, amount of drugdelivered, status of the drug delivery for each drug channel, time,percent complete, percent remaining, time remaining, time delivered,date, patient ID, patient name, alarms, alerts, etc. Such userinterfaces can include a color graphical display. In certainimplementations, for example, the user interface is color codedaccording to drug, dosing, or status of drug delivery (e.g., done,running, ready, etc.).

The drug delivery device 103 also includes an alarm and/or alert systemto which the control unit of the drug delivery device 103 is connected.The alarm and/or alert system can be configured to emit a visual and/oraudio alarm and/or alert. The alarm and/or alert system can furtherinclude pre-programmed alarm and/or alert limitations so that when auser modifies any aspect of the system to be outside of the limitations,or the machine itself detects any aspects of the system to be outside ofthe limitations, the module emits an alarm and/or alert.

FIG. 3 shows one of the vials 116, 118 and its associated drug vialspike 120 and feeder line 122 in a disconnected state. As shown, thedrug vial 116, 118 includes a cap (also referred to as a sleeve) 119secured to a neck portion 121 of the vial. A rubber seal 123 ispositioned between the cap 119 and the neck portion 121. A body portion125 of the vial is integrally connected to the neck portion 121.Typically, each of the feeder lines 122 and the drug vial spikes 120includes mating luer lock connectors that permit the feeder lines 122 tobe easily connected to and disconnected from the drug vial spikes 120.Alternatively, the feeder lines 122 can be permanently attached to thedrug vial spikes 120. The feeder lines 122 can, for example, be weldedor adhesively bonded to the drug vial spikes 120.

Each of the drug vial spikes 120 is configured to grasp and releasablyretain the cap 119 of its associated drug vial 116, 118. As shown inFIGS. 4-6, the drug vial spike 120 is a cup-shaped member with a centralspike 136 extending from a central region of a base 138 of thecup-shaped member. The central spike 136 includes a relatively sharp tip142 and forms a channel 140 (shown in FIG. 6) that extends along thelength of the central spike 136. During use, the central spike 136 isinserted into its associated drug vial 116, 118 by piercing the rubberseal 123 of the drug vial 116, 118. The user can, for example, grasp thedrug vial 116, 118 and press it downward onto the drug vial spike 120 inorder to cause the central spike 136 to pierce the rubber seal 123 ofthe vial 116, 118. The channel 140 of the central spike 136 allows thecontents of the drug vial 116, 118 to flow out of the drug vial 116, 118via the central spike 136. An outer surface of the central spike 136also forms channels or slots 144, 146 that extend along the centralspike 136 to facilitate flow of the drug into the central channel 140.

The base 138 of the cup-shaped drug vial spike 120 includes multipleleaf springs 152. The leaf springs 152 are resilient members that arebiased upward (i.e., in the direction of the drug vial 116, 118 when thedrug vial 116, 118 has been loaded onto the drug vial spike 120). Theleaf springs 152 are disposed over apertures 154 formed in the base.When the drug vial 116, 118 is loaded into place, each leaf spring 152is depressed, allowing the top edge of the vial cap 119 to temporarilylock into place under an annular flange 150 formed by the side wall ofthe drug vial spike 120. The resilient leaf springs 152 provide forretraction of the central spike 136 relative to the vial 116, 118 afterthe spike 136 has been fully inserted into the vial 116, 118 (i.e.,after the cap 123 of the vial 116, 118 has contacted the base 138 of thedrug vial spike 120). Because the resilient leaf springs 152 are biasedtoward the drug vial 116, 118, after the drug vial 116, 118 is loadedonto the central spike 136 by deforming the leaf springs 152 inwardtoward the base 138, the leaf springs 152 force the vial 116, 118 backaway from the base 138. Due to the friction forces between the rubberseal 123 of the vial 116, 118 and the central spike 136 of the drug vialspike 120, the portion of the rubber seal 123 contacting the centralspike 136 moves away from the base 138 of the drug vial spike 120 to alesser extent than the remainder of the vial 116, 118 when this outwardforce is applied to the drug vial 116, 118. In certain implementations,for example, the portion of the rubber seal 123 contacting the centralspike 136 does not move at all in response to the outward forces of theleaf springs 152. Because the portion of the rubber seal 123 in contactwith the central spike 136 moves a shorter distance relative to the drugvial spike 120 than the remainder of the vial 116, 118, the centralportion of the rubber seal 123 tends to bulge away from the vial 116,118, and the central spike 136 remains embedded in the vial 116, 118 andable to access the drug or fluid contained therein. The rubber seal 123can, for example, form a concave shape or dish shape, which helps toensure that the full contents of the drug vial 116, 118 are evacuatedfrom the vial.

By helping to ensure that the full contents of the drug vial 116, 118are evacuated, the drug vial spike 120 provides significant advantagescompared to certain conventional spikes and syringes. For example, whenmany conventional spikes or syringes puncture the rubber seal of a drugvial, the spike or syringe pushes portions of the rubber sealsurrounding the spike or syringe inward. As a result, medication maybecome adhered to or get lodged behind the surface of the inwardlyfolded portion of the rubber seal. As a result, some of the drug becomestrapped within the vial and is not used. The trapped portion of the drugis typically discarded with the vial. Certain drugs, such as Epogen®,are very expensive, and thus even one droplet left behind in the vialcan be worth a significant price to the patient and/or care provider,especially over the course of multiple treatments. Thus, the drug vialspikes 120 described herein can save patients and/or care providers asignificant amount of money over time and can ensure that life-savingdrugs are not wasted. In addition, the drug vial spikes 120 can increasethe accuracy with which prescribed drug dosages are delivered topatients, which can improve patient health.

Still referring to FIGS. 4-6, the drug vial spike 120 also includesmultiple bi-stable members 148 positioned around the central spike 136of the drug vial spike 120. As provided to the user, the bi-stablemembers 148 are in a first position (i.e., deformed away from the base138 into the drug vial recess). Apertures sized and shaped to allow thebi-stable members 148 to pass therethrough are provided in the base 138below the bi-stable members 148. The bi-stable members 148 areconfigured to snap into a second position (i.e., deformed away from thebase 138 and out of the drug vial recess) when forces of a givenmagnitude in a direction opposite the vial 116, 118 are applied to themembers. As a result, when the vial 116, 118 has been properly seatedwithin the vial recess of the drug vial spike 120, the drug vial appliesa force to each of the bi-stable members 148, causing the bi-stablemembers 148 to snap into this second position. In this second position,at least a portion of each bi-stable member 148 protrudes beyond thebottom surface of the base 138 opposite the vial. Thus, the bi-stablemembers 148 provide visual confirmation to the user that the vial isproperly seated within the vial recess of the drug vial spike 120.

As shown in FIGS. 3 and 6, the circumferential side wall of the drugvial spike 120 extends to a slightly greater height than the centralspike 136. This configuration, in addition to helping secure the drugvial within the cavity formed by the drug vial spike 120, helps toensure that the central spike 136 is not inadvertently contacted (e.g.,by the operator) prior to loading of a drug vial onto the spike. Thiscan, for example, help to prevent the central spike 136 from beingcontaminated before it is inserted into the drug vial.

In some implementations, the drug vial spikes 20 are formed of one ormore medical grade plastics, such as PVC or acrylonitrile butadienestyrene (ABS). However, other medical grade plastics can be used to formthe drug vial spike 120. Similarly, certain metals, such as stainlesssteel, could be used to form the drug vial spike 120.

Epogen® is provided in two single-dose 1 ml vials with variousconcentrations and two multi-dose vials with two differentconcentrations. The contents of each of these vials are described below.

Single-dose, Preservative-free Vial—1 mL (2,000, 3,000, 4,000, or 10,000Units/mL). Each 1 mL of solution contains 2,000, 3,000, 4,000 or 10,000Units of Epoetin alfa, 2.5 mg Albumin (Human), 5.8 mg sodium citrate,5.8 mg sodium chloride, and 0.06 mg citric acid in Water for Injection,USP (pH 6.9±0.3). This formulation contains no preservative.

Single-dose, Preservative-free Vial—1 mL (40,000 Units/mL). Each 1 mL ofsolution contains 40,000 Units of Epoetin alfa, 2.5 mg Albumin (Human),1.2 mg sodium phosphate monobasic monohydrate, 1.8 mg sodium phosphatedibasic anhydrate, 0.7 mg sodium citrate, 5.8 mg sodium chloride, and6.8 mcg citric acid in Water for Injection, USP (pH 6.9±0.3). Thisformulation contains no preservative.

Multidose, Preserved Vial—2 mL (20,000 Units, 10,000 Units/mL). Each 1mL of solution contains 10,000 Units of Epoetin alfa, 2.5 mg Albumin(Human), 1.3 mg sodium citrate, 8.2 mg sodium chloride, 0.11 mg citricacid, and 1% benzyl alcohol as preservative in Water for Injection, USP(pH 6.1±0.3).

Multidose, Preserved Vial—1 mL (20,000 Units/mL). Each 1 mL of solutioncontains 20,000 Units of Epoetin alfa, 2.5 mg Albumin (Human), 1.3 mgsodium citrate, 8.2 mg sodium chloride, 0.11 mg citric acid, and 1%benzyl alcohol as preservative in Water for Injection, USP (pH 6.1±0.3).

Thus, Epogen® vials are provided in the following standardconcentrations: 2,000 units per vial, 3,000 units per vial, 4,000 unitsper vial, 10,000 units per vial, 20,000 units per vial, and 40,000 unitsper vial.

The prescribed dosage of Epogen® is individualized for each patient ondialysis, and the prescribed dosage can vary dramatically from onepatient to another. However, it has been found that by using from one tothree full vials in various different combinations, over 90 percent ofpatient dosage requirements can be fulfilled. The drug delivery devicecan be operated in a manner to provide any of various different discretedosages between 0 and 20,000 units with various different combinationsof three vials, and can thus be used to treat over 90 percent ofdialysis patients without having to change vials during use or usecustomized Epogen®. In addition, because substantially all of theEpogen® is drained from each of the vials that is used, very little, ifany, Epogen®, which is a very expensive drug, is wasted.

The Epogen® dosing schedule described below can be used by the operatorof the drug delivery device to reduce or minimize waste of Epogen®. Thedosing schedule has been developed to give guidance to the prescribersuch that the correct average dose can be administered usingpermutations of three vials per treatment and permutations of threeweekly treatments. The permutations can be weighted by the measure ofdosage variation (standard deviation) or by the minimum number of vialsselected.

Table 1 below illustrates that each of the drug channels of the drugvial holder of the drug delivery device can be loaded with a vialcontaining 2,000 units of Epogen®, 3,000 units of Epogen®, 4,000 unitsof Epogen®, 10,000 units of Epogen®, 20,000 units of Epogen®, or 40,000units of Epogen®, or with no vial at all.

TABLE 1 Vial 1 Vial 2 Vial 3 0 0 0 2000 2000 2000 3000 3000 3000 40004000 4000 10000 10000 10000 20000 20000 20000 40000 40000 40000

In many cases, a desired Epogen® delivery amount for a single treatmentwill not equal the amount of Epogen® that is currently manufactured andprovided in a single vial. In those cases, two or more vials of Epogen®need to be used to deliver the desired amount. There are multiplepermutations that satisfy some of these unique delivery amountrequirements. Table 2 below shows these various permutations for asingle treatment. In particular the first three columns of the tableshow the three vials used in each permutation, the fourth column showsthe total amount delivered by using those particular three vials, thefifth column shows the standard deviation (i.e., the volume varianceexperienced throughout the treatment as a result of using the threedifferent vials (the difference between the sum of the volumes and theaverage volume)), and the sixth column shows the total number of vialsused during the treatment.

TABLE 2 Total Num Vial 1 Vial 2 Vial 3 Dose Stdev Vials 0 0 0 0 0 0 20000 0 2000 1155 1 3000 0 0 3000 1732 1 2000 2000 0 4000 1155 2 4000 0 04000 2309 1 3000 2000 0 5000 1528 2 3000 3000 0 6000 1732 2 4000 2000 06000 2000 2 2000 2000 2000 6000 0 3 4000 3000 0 7000 2082 2 3000 20002000 7000 577 3 4000 4000 0 8000 2309 2 3000 3000 2000 8000 577 3 40002000 2000 8000 1155 3 4000 3000 2000 9000 1000 3 3000 3000 3000 9000 0 310000 0 0 10000 5774 1 4000 4000 2000 10000 1155 3 4000 3000 3000 10000577 3 4000 4000 3000 11000 577 3 10000 2000 0 12000 5292 2 4000 40004000 12000 0 3 10000 3000 0 13000 5132 2 10000 4000 0 14000 5033 2 100002000 2000 14000 4619 3 10000 3000 2000 15000 4359 3 10000 4000 200016000 4163 3 10000 3000 3000 16000 4041 3 10000 4000 3000 17000 3786 310000 4000 4000 18000 3464 3 10000 10000 0 20000 5774 2 20000 0 0 2000011547 1 20000 2000 0 22000 11015 2 10000 10000 2000 22000 4619 3 200003000 0 23000 10786 2 10000 10000 3000 23000 4041 3 20000 4000 0 2400010583 2 20000 2000 2000 24000 10392 3 10000 10000 4000 24000 3464 320000 3000 2000 25000 10116 3 20000 4000 2000 26000 9866 3 20000 30003000 26000 9815 3 20000 4000 3000 27000 9539 3 20000 4000 4000 280009238 3 20000 10000 0 30000 10000 2 10000 10000 10000 30000 0 3 2000010000 2000 32000 9018 3 20000 10000 3000 33000 8544 3 20000 10000 400034000 8083 3 20000 20000 0 40000 11547 2 40000 0 0 40000 23094 1 2000010000 10000 40000 5774 3 40000 2000 0 42000 22539 2 20000 20000 200042000 10392 3 40000 3000 0 43000 22279 2 20000 20000 3000 43000 9815 340000 4000 0 44000 22030 2 40000 2000 2000 44000 21939 3 20000 200004000 44000 9238 3 40000 3000 2000 45000 21656 3 40000 4000 2000 4600021385 3 40000 3000 3000 46000 21362 3 40000 4000 3000 47000 21079 340000 4000 4000 48000 20785 3 40000 10000 0 50000 20817 2 20000 2000010000 50000 5774 3 40000 10000 2000 52000 20033 3 40000 10000 3000 5300019655 3 40000 10000 4000 54000 19287 3 40000 20000 0 60000 20000 2 4000010000 10000 60000 17321 3 20000 20000 20000 60000 0 3 40000 20000 200062000 19009 3 40000 20000 3000 63000 18520 3 40000 20000 4000 6400018037 3 40000 20000 10000 70000 15275 3 40000 40000 0 80000 23094 240000 20000 20000 80000 11547 3 40000 40000 2000 82000 21939 3 4000040000 3000 83000 21362 3 40000 40000 4000 84000 20785 3 40000 4000010000 90000 17321 3 40000 40000 20000 100000 11547 3 40000 40000 40000120000 0 3

The operator can consult the above table to determine the most desirablecombination of vials. The operator may, for example, select thecombination that requires the fewest vials to deliver the desired amountof drug for the treatment. The user may alternatively select thecombination of vials based on the variation in drug delivery amountthroughout the drug delivery process or the amount of time required todeliver the drug (not shown in the table above).

This vial selection strategy can also be extended to permutations of thetreatment doses to give an average weekly dose with better resolution.For example, with the above combinations, the same permutation schedulecan be used to achieve an average weekly dose. In Table 3 below, thefirst three columns show the dosage used for each of three weeklytreatments, the fourth columns shows the average dosage achieved overthose three weekly treatments, and the fifth column shows the standarddeviation (i.e., the variance in dosage over the three weekly treatments(the difference between the sum of the dosages and the average dosage)).

TABLE 3 Treatment Dosage Average (3 Treatments per Week) Dosage Stdev2000 2000 2000 2000 0 2000 2000 3000 2333 577 2000 3000 2000 2333 5773000 2000 2000 2333 577 2000 2000 4000 2667 1155 2000 3000 3000 2667 5772000 4000 2000 2667 1155 3000 2000 3000 2667 577 3000 3000 2000 2667 5774000 2000 2000 2667 1155 2000 2000 5000 3000 1732 . . . . . . . . . . .. . . . 20000 20000 17000 19000 1732 18000 20000 20000 19333 1155 2000018000 20000 19333 1155 20000 20000 18000 19333 1155 20000 20000 2000020000 0

The above tables can be consulted to minimize the number of vials usedper week while maintaining the dosage variation over the three weeklytreatments within an acceptable range. As an example, if the prescribeddosage is 16,000 units of Epogen®, the user first consults Table 2 aboveto determine which combinations of vials add up to this dosage. Table 2above shows that the user can use: one 10,000 unit vial, one 4,000 unitvial, and one 2,000 unit vial; or one 10,000 unit vial and two 3,000unit vials. Thus, the fewest number of vials that the user could use forthe treatment would be three vials. This would mean that nine vials wererequired per week (three vials per treatment and three treatments perweek). However, the user can then consult Table 3 above to determinewhether it is possible to reduce the number of vials used per week byfocusing on the average dosage per week as opposed to the dosage perindividual treatment. To do this, the user would look to Table 3 todetermine the different treatment dosages that could be used for each ofthe three weekly treatments in order to achieve an average dosage of16,000 units. If any of those options had a standard deviation (ordosage variance) that was below an acceptable maximum dosage variance,the user would look back to the first table to determine the vialcombinations that could be used to achieve each of those treatmentdosages. Based on those vial combinations, the user could determine thetotal number of vials that would be required for the week and comparethat number to the total number of required vials determined from Table2 (i.e., nine vials). If any of the alternative vial combinations resultin fewer than nine vials per week, then the user could use the dosingschedule provided by Table 3.

Although Epogen® dosages are generally prescribed based on a singletreatment, Table 3 above can be consulted by physicians when prescribingEpogen® and those physicians can prescribe dosages that are provided onthe table. Prescribing Epogen® in this manner can help to ensure thattreatments can be carried out on average with fewer vials and can thusreduce the amount of material (e.g., used vials) that need to bediscarded after treatment and the inventory of vials that need to bemaintained. In addition, by purchasing the same volume of drug in fewervials, the overall cost of that drug can be reduced.

While Table 3 above relates to treatments over a period of one week,similar tables can be prepared and consulted for any of various othertime periods (e.g., two weeks, one month, two months, six months, etc.).

The calculations described above relating to maximizing the effectivedosages of Epogen® may be used for other drugs as well. For example, adosing schedule of the type described above can be used to determine themost desirable approach for delivering the Venofer® over multipletreatments. Unlike Epogen®, however, Venofer® is relatively inexpensive,so it is generally of less concern from a cost standpoint to minimizethe number of vials of Venofer® used over a given period of time (e.g.,one week or one month). However, such a dosing schedule can reduce(e.g., minimize) the amount of materials (e.g., used vials) to bediscarded and can reduce the effort and time required to set up thedevice for drug delivery.

The above-described dosing schedules can be provided to the user in anyof various different formats. In some implementations, the tables aresimply printed on a document (e.g., a user manual, a laminated card,etc.) that the user can consult during treatment. In certainimplementations, the tables are provided to the user in the form ofelectronic files that can be saved to a computer or viewed online.

In some implementations, the dosing schedule is provided as a computerprogram installed in the drug delivery device 103. In suchimplementations, the user would input the prescribed dosage informationand the control unit of the drug delivery device 103 would display therelevant portions of the tables on the user interface. The user couldthen examine the displayed portions of the tables on the user interfaceand, based on that displayed information, determine a desirablecombination of vials to use for the treatment. Alternatively oradditionally, the computer program could be designed to automaticallydetermine the best combination of vials to use for the treatment (e.g.,based on preferences input by the user) and display that vialcombination for the user.

Referring to FIGS. 1 and 7, prior to beginning hemodialysis treatment ona patient, the various lines that make up the blood circuit anddialysate circuit of the hemodialysis machine are primed, and then thepatient lines 105 are connected to the patient. After connecting thepatient lines 105 to the patient, the blood pump 108 is activated tocirculate blood through the blood circuit. A dialysate pump is alsoactivated to pump dialysate through the dialysate circuit of thehemodialysis machine. The blood is drawn from the patient and deliveredto the drip chamber 106 via the arterial patient line. The drip chamber106 acts as an air trap such that any air in the blood is released asthe blood passes through the drip chamber 106. In particular, the dripchamber 106 includes a vent through which air released from the bloodcan be vented from the drip chamber 106. The blood is then pumped fromthe drip chamber 106 to the dialyzer 110, which includes asemi-permeable membrane that divides the dialyzer 110 into two chambers.As the blood passes through one of the chambers of the dialyzer 110,dialysate from the dialysate circuit passes through the other chamber.As the blood flows by the dialysis fluid, impurities, such as urea andcreatinine, diffuse through the semi-permeable membrane into thedialysate. The spent dialysate is either disposed of or recycled andreused. The cleansed blood exiting the dialyzer 110 is returned to thepatient via the venous patient line.

Since the drug delivery process is usually shorter than the overallhemodialysis process, the set up of the drug delivery device 103 and itsassociated components typically occurs after hemodialysis treatment hasbegun. In order to prepare the drug delivery device 103 for use, theuser first determines the prescribed Epogen® dose and then consults adosing schedule for the different vial combinations that can be used todeliver the prescribed Epogen® dose. The user then selects one of theEpogen® vial combinations provided based on the user's preference. Theuser can, for example, choose the vial combination that requires thefewest number of vials for the upcoming treatment or for multipletreatments over a given time (e.g., one week, one month, etc.), or thevial combination that provides the most consistent amount of drugdelivered per treatment (e.g., based on one week worth of treatments,one month worth of treatments, etc.). Alternatively, the user canconsider both the number of vials required and the consistency of thedrug amount delivered over a given number of treatments to select a vialcombination. As discussed above, in certain implementations, the bestcombination of vials (based on the user's preferences) is automaticallydisplayed on the user interface for the user to read. After choosing adesired combination, the user gathers the necessary Epogen® vials from avial storage supply (e.g., a refrigerator).

The user then connects the disposable drug administration fluid line set107, which includes the drug vial spikes 120, the drug feeder lines 122,and the drug delivery line 104, to the drug delivery device 103. Thedrug administration fluid line set 107 is typically provided to the userin a sterile bag. To connect the drug administration fluid line set 107to the drug delivery device 103, the user first opens the sterile bagand removes the drug administration fluid line set 107. The user thenpositions each of the drug vial spikes 120 within one of the drugchannels 114 of the drug vial holder 112, threads the feeder lines 122through their respective bubble detectors 128 and occluders 130, andconnects the drug delivery line 104 to the drip chamber 106 using anaseptic technique. This last step typically involves connecting a luerlock fitting on the end of the drug delivery line 104 to a mating luerlock fitting on a drip chamber level adjust line extending from the dripchamber 106. However, other types of connectors can be used.

Once the drug administration fluid line set 107 is in place, theVenofer® vial 116 and Epogen® vials 118 are loaded into the channels 114of the drug vial holder 112. In particular, each vial 116, 118 isinverted and inserted into its associated channel 114 so that thecentral spike 136 of the associated drug vial spike 120 pierces therubber seal 123 of the vial 116, 118. As discussed above, thisarrangement allows the drug within the vial 116, 118 to pass through thedrug vial spike 120 and into the feeder line 122 connected to the drugvial spike 120. Use of the drug vial spikes 120 is advantageous becausethe drugs can be directly delivered from their sterile vial 116, 118without using an intermediary needle to transfer the drug from the vial116, 118 to the patient.

While FIG. 1 illustrates the use of four vials (i.e., one Venofer® vial116 and three Epogen® vials 118) in the four-channel vial holder 112, itshould be understood that fewer vials may be used, depending on theprescribed dosage requirement and the operator's preferences. In suchcases, one or more of the drug vial holder's channels 112 would simplybe empty (i.e., no drug vial would be disposed in one or more of thechannels 112).

After loading the Venofer® and Epogen® vials 116, 118, the prescribeddosages of Venofer® and Epogen® are entered into the drug deliverydevice 103 using the user interface 134. As discussed below, it is oftenthe case that the full amount of Venofer® in the Venofer® vial is notrequired to achieve the prescribed dosage. Therefore, it may beimportant to input the prescribed dosage of Venofer® to ensure that theproper amount of Venofer® is delivered to the patient. On the otherhand, the combination of Epogen® vials generally amount to theprescribed Epogen® dosage. Thus, even without entering the prescribedEpogen® dosage, the prescribed dosage should be achieved by simply fullyevacuating each of the Epogen® vials 118. Entering the prescribedEpogen® dosage, however, can enable the drug delivery device 103 toconfirm that the actual amount of Epogen® delivered from the vials isequal to the prescribed Epogen® dosage.

After entering the prescribed dosages of Venofer® and Epogen®, each ofthe feeder lines 122 is primed. Priming can be an automated process thatbegins after the operator confirms that the vials have been loaded(e.g., by pressing a button on the user interface 134) or after the drugdelivery device 103 confirms that all necessary vials are in place. Toprime the feeder lines 122, the drug pump 132 is activated and theoccluders 130 are sequentially opened. Each occluder 130 remains openfor a predetermined time after the drug from its associated vial isdetected by the bubble detector 128. After detection of the drug by theair bubble detector 128 associated with the Venofer® vial 116 (i.e., thefirst vial that is to be emptied during the drug delivery process), thedrug pump 132 continues to operate and the occluder 130 associated withthe feeder line 122 connected to that vial remains open for a sufficientperiod of time to cause the Venofer® to substantially fill the drugdelivery line 104. Substantially filling the feeder line with theVenofer® ensures that as additional Venofer® is drawn from the vial 116,Venofer® will enter the drip chamber 106. After filling the drugdelivery line 104 with the Venofer®, the occluder 130 associated withthe feeder line 122 connected to the vial 116 pinches that feeder line122 and one of the other occluders 130 is opened to prime the feederline 122 associated with the open occluder 130. This process is repeateduntil each of the feeder lines 122 has been primed.

If the drug is not detected by one of the air bubble detectors 128during the priming process, an alarm is activated. This indicates aproblem with either the drug delivery device 103 (e.g., the bubbledetector 128 of the drug delivery device 103) or the drug administrationfluid line set 107 (e.g., the drug vial spike 120 or feeder line 122 ofthe drug administration fluid line set 107). In response to the alarm,the user typically replaces the drug administration fluid line set 107or adjusts the drug administration fluid line set 107 and repeats theprocess.

Priming the feeder lines in this manner is advantageous in that itincreases the probability of the clinician (if being used in a clinicsetting) being nearby to quickly replace the drug administration fluidline set 107 if a malfunction is detected. Without priming the feederlines 122, for example, a defect in the administration set might not bedetected until the middle of the drug delivery process when the drug isfirst pulled from the drug vial associated with the portion of the drugadministration fluid line set 107 including the defect. In that case,the treatment would have to be stopped until the clinician made his orher way over to the machine to rectify the problem.

After priming the feeder lines 122, Venofer® is delivered from theVenofer® vial 116 to the drip chamber 106 where it mixes with thepatient's blood. The Venofer® is delivered to the patient by opening theoccluder 130 associated with the Venofer® vial 116 (while leaving all ofthe other occluders 130 closed) and running the drug pump 132. Venofer®is a relatively inexpensive drug, so it is less important to ensure thatall of the Venofer® is fully evacuated from the vial 116, as compared tothe Epogen®. In some cases, the prescribed dosage of the Venofer® willbe less than the amount of Venofer®contained in the vial 116 such thatsome of the Venofer® will remain in the vial after prescribed volume ofthe drug is delivered. The volume of Venofer® delivered to the patientis monitored and controlled by the control unit and the drug pump 132 ofthe drug delivery device 103. The peristaltic drug pump 132 works bycompressing the drug delivery line 104 and moving a “pillow” of fluidthat is pinched between two points of the drug delivery line 104 by thepump rollers. Each “pillow” of fluid is of a volume determined by theroller spacing and the inside diameter of the drug delivery line 104.When the pump 132 operates at a given speed, a series of these “pillow”shaped volumes of fluid are delivered to the drip chamber 106. Bychanging the speed of the pump 132, the rate of fluid delivery ischanged. The pump speed can be controlled by adjusting the voltagedelivered to the pump 132. The voltage delivered to the motor of thepump 132 can, for example, be adjusted by the control unit (e.g.,software of the control unit) until the correct speed (i.e., the speedthat corresponds to the desired flow rate) is measured on the encoder.

As discussed above, the drip chamber 106 of the hemodialysis system 100functions as an air trap. Thus, any gases (e.g., air) introduced intothe system (for example, air drawn in from one of the vials 116, 118)are able to escape from the drug and blood within the drip chamber 106.In addition to removing air from the system, the drip chamber 106provides other benefits. For example, the drip chamber 106 providesvisual confirmation of drug delivery and allows the delivered drug tomix with the patient's blood prior to reaching the patient. In addition,the drip chamber 106 allows for simple luer connection to the drugadministration fluid line set 107. As a result, the patient need not bestuck with an additional needle in order to receive the drugs from thevials 116, 118.

FIG. 8 illustrates a series of user interface screen shots during theVenofer® delivery processes. As shown, the user interface displays theprescribed dosage and the dosage delivered. When the dosage delivered isequal to the prescribed dosage, that indicates to the user that theVenofer® delivery process is complete. In situations where theprescribed dosage of Venofer® exceeds the number of units provided inthe vial, the status would alternatively read “Replace Vial” afterdelivering the full contents of the first vial. This would prompt theoperator to replace the first Venofer® vial with a second Venofer® inorder to enable the prescribed dosage to be achieved. Upon determiningthat the prescribed dosage of Venofer® has been delivered to the dripchamber 106, the control unit causes the occluder 130 associated withthe Venofer® feeder line to be closed.

Venofer® reaches its full potential through precise delivery over anextended period of time. With controlled drug infusion using theperistaltic drug pump 132 and the drip chamber 106, the Venofer® can bedelivered at a precise rate that will keep the drug concentration withinthe therapeutic margin and out of the toxic range. The peristaltic drugpump 132 is able to provide appropriate drug delivery to the patient ata controllable rate, which does not require frequent medical attention.

Referring again to FIGS. 1 and 7, after the desired amount of Venofer®has been delivered to the drip chamber 106 and its associated occluder130 has been closed, the occluder 130 associated with the first Epogen®vial 118 (i.e., the Epogen® vial directly to the right of the Venofer®vial 116) is opened such that Epogen® is delivered to the drip chamber106. The combination of Epogen® vials 118 has been selected so that theprescribed dosage of Epogen® is equal to the Epogen® contained in thethree Epogen® vials 118. Thus, it is not generally necessary to monitorthe volume of Epogen® delivered to the drip chamber 106. However, inmany cases, the peristaltic drug pump 132 (or the control unit that isconnected to the drug pump 132) monitors the amount of Epogen® deliveredto confirm that the amount of Epogen® delivered is equal to theprescribed amount. This can, for example, help to identify a situationin which an incorrect Epogen® vial was used (e.g., due to user error ormislabeling). Because the full volume of the Epogen® vial 118 is to beused, the occluder 130 associated with the Epogen® vial 118 is simplykept open until the bubble detector 128 detects an air bubble in thefeeder line 122, indicating that the full volume of Epogen® wasevacuated from the vial 118 (i.e., indicating that the vial 118 isempty). When the bubble detector 128 detects air in the feeder line 122,a signal is sent to the control unit, indicating that the first Epogen®vial 118 is empty. The control system then sends a signal to theoccluder 130 associated with the first Epogen® vial 118 to clamp off thefeeder line 122 associated with the first Epogen® vial 118 afterassuring that an additional known volume is pumped so that the Epogen®in the line downstream of the bubble detector 128 is flushed down to asegment where the Epogen® from the next vial can push that Epogen®remaining in the line to the drip chamber 106. In particular, thecontrol unit ensures that the additional pumped volume is sufficient topush the Epogen® past the occluder 130 such that the next volumedelivered will push the Epogen® into and through the drug delivery line104 to the drip chamber 106. The control unit also sends a signal to theoccluder 130 associated with the second Epogen® vial 118 (i.e., theEpogen® vial directly to the right of the first Epogen® vial) to openthe feeder line 122 associated with the second Epogen® vial 118. TheEpogen® delivery process described above is then repeated for the secondand third Epogen® vials.

FIG. 9 is a screen shot of the user interface 134 of the drug deliverydevice 103 during the delivery of Epogen® from the first Epogen® vial118. As shown, the portion of the display dedicated to the Venofer® vialindicates that the full prescribed dosage of the Venofer® has beendelivered and that the Venofer® delivery process is thus complete. Theportion of the screen dedicated to the first Epogen® vial indicates thatthe Epogen® from that vial is in the process of being delivered to thepatient. In particular, it shows that 500 units of the 4,000 unit vialhave been delivered. The screen further shows that delivery for thesecond and third Epogen® vials has not yet begun and that each of thosevials contains 1,000 units of Epogen®. In treatments where fewer thanthree Epogen® vials are to be delivered, the portion of the screendedicated to the missing vials would indicate that no drug is to bedelivered from that/those channel(s).

As discussed above, the design of the drug vial spikes 120 helps toensure that the Venofer® and Epogen® vials 116, 118 are fully evacuatedduring treatment. In particular, the outward bulge created in the rubberseal 123 of each vial 116, 118 creates a dish-shaped recess along theinner surface of the rubber seal 123. This recess functions as a funnelto ensure that substantially all of the drug flows out of the vial 116,118 and into the feeder line 122. Traditionally, drug vials have beenfilled in a manner to include a slightly greater volume of drug in thevials than the vial label indicates. This has been due to the inabilityof conventional drug delivery mechanisms to evacuate all of the drugfrom the vial. The drug vial spikes 120 described herein can help toprevent the drug from being trapped in the vial and discarded with thevial. Thus, the vials 116, 118 used in the drug delivery system 102 neednot be overfilled.

After delivering the desired amounts of Venofer® and Epogen®, the drugdelivery device 103 is deactivated and the drug administration fluidline set 107 and vials 116, 118 are removed from the drug deliverydevice 103 and discarded.

In some implementations, between each transition from one vial to thenext, an air bubble is pulled into the drug delivery line 104 via thefeeder line 122. In particular, air is pulled into the feeder line 122from the newly empty vial, and the resulting air bubble is delivered tothe drip chamber 106, where the air bubble is removed from the system.As the air bubble moves from the feeder line 122 to the drip chamber106, it clears any remaining medicament from the previously used vialout of the feeder line 122, the drug delivery line 104, and the variouslines and connections therebetween. This helps to ensure that all of thedrug evacuated from the vial is delivered to the patient. It alsoreduces (e.g., eliminates) mixing of two distinct drugs that aredelivered by the same line running through the same/singular pump. Manydrugs may cause an adverse reaction by the patient if they are mixedprior to delivery to the patient. This techniques is advantageous inthat it can help to prevent mixing of such drugs before they reach thepatient's blood.

In certain implementations, the control unit operates the components ofthe drug delivery device 103 in a manner so that an air bubble is passedthrough the feeder line 122, the drug delivery line 104, and the linesegments and connection positioned therebetween only between vials thatcontain incompatible drugs. For example, the control system may allow anair bubble to pass through the bubble detector 128 and the occluder 130toward the drug delivery line 104 if the control unit detects anothervial of a different medication in the next drug channel. Thus in theexemplary method described above, an air bubble would be passed throughthe feeder line 122 associated with the Venofer® vial 116 and beyond theoccluder 130 after delivery of the prescribed amount of Venofer® but nosuch air bubbles would be passed through the lines to the drip chamberwhen transitioning between the three Epogen® vials 118.

It has been found that having a relatively small inner diameter improvesthe ability of the air bubble to remove substantially all of the drugfrom the feeder lines and drug delivery line. In some implementations,the feeder lines 122, the drug delivery line 104, and the line segmentsand connectors therebetween have inside diameters of about 0.030 inchand outside diameters of about 0.125 inch. However, the lines andconnectors can have different dimensions that are suitable for thisprocess.

In certain implementations, the operating speed of the pump 132 isgradually increased as the quantity of drug in the vial 116, 118 fromwhich the drug is being drawn decreases. As the quantity of drug in thatvial decreases, a slight vacuum is produced in the vial. This vacuum canresult in a decreased flow rate of the drug from the vial if the pumpspeed remains constant. Thus, gradually increasing the pump speed as thedrug is drawn from the vial can help to maintain a substantiallyconstant flow rate of the drug from the vial throughout the drugdelivery process.

While certain implementations have been described, other implementationsare possible.

While the top surfaces of the bi-stable members 148 have beenillustrated as being substantially smooth, in certain implementations,each of the bi-stable members 148 is provided with a raised feature(e.g., a raised member) that extends from its top surface. The raisedfeature can help to ensure that the insertion of the drug vial into thedrug vial recess of the drug vial spike 120 moves the bi-stable member148 a sufficient distance into its associated aperture to cause thebi-stable member 148 to snap into the second position. The projectioncan, for example, be an elongate rod that has a sufficient length orheight to ensure that the bi-stable member is pushed far enough downinto its associate opening in the base 138 of the drug vial spike 120 tocause the bi-stable member to snap into the second position when thedrug vial 116, 118 is fully inserted into the vial recess of the drugvial spike 120 (e.g., when the cap 119 of the drug vial 116, 118contacts the base 138 of the drug vial spike 120).

While the surfaces of the leaf springs 152 that are contacted by thedrug vial spike 120 when the drug vial 116, 118 is loaded onto the drugvial spike 120 have been illustrated as being substantially smooth, incertain implementations, a pointed projection extends from the surfaceof each leaf spring 152. The leaf spring 152 can provide sufficientresistance to deflection and the projections can be sufficiently pointedto dent the cap 119 of the vial 116, 118 into the rubber seal 123 whenthe operator presses the vial 116, 118 downward against the leaf springs152 to load the drug vial 116, 118 onto the drug vial spike 120. Incertain implementations, the leaf springs 152 each provide a resistanceforce of about 1 pound to about 20 pounds (e.g., about 1 pound to about10 pounds, about 1 pound to about 5 pounds, about 5 pounds to about 10pounds) prior to deflecting toward the base 138 of the drug vial spike120.

While the drug vial spike 120 has been described as including leafsprings 152 to force the drug vial 116, 118 away from the base 138 ofthe drug vial spike 120 after insertion of the drug vial 116, 118, othertypes of springs, such as coil springs, can be used. The springs can beseparate components that are attached to the drug vial spike (e.g., thebase or side wall of the drug vial spike) or can be integrally formedwith the drug vial spike (e.g., the base or side wall of the drug vialspike).

While the drug vial spike 120 has been described as including a flangethat releasably holds the drug vial 116, 118, other temporary viallocking mechanisms or techniques including but not limited to clips,clamps, plastic friction slip fits, elastomeric cap fits, magneticclamps, vial neck clips or clamps, vial body spring clips, bungee cords,etc. can be used.

While the central spike 136 of the drug vial spike 120 discussed aboverelies only on friction between its peripheral surface and the rubberseal 123 of the vial 116, 118 to pull the rubber seal 123 outward, othertechniques are possible. In certain implementations, as shown in FIG.10, a central spike 236 of a drug vial spike 220 includes an enlargedcone-shaped tip 242. After the conical tip 242 of the central spike 236is inserted into the drug vial 116, 118 and the vial is pushed away fromthe drug vial spike 220 by the springs 152 extending from the base 138of the drug vial spike 220, the conical tip 242 engages the innersurface of the rubber seal 123 of the vial 116, 118. This constructionhelps to ensure that the central portion of the rubber seal 123 ispulled away from the vial 116, 118 to create a depression along theinner surface of the rubber seal 123 of the inserted vial. As a result,this construction helps to ensure that all of the drug contained withinthe vial 116, 118 can be evacuated.

While the enlarged tip 242 of the spike 236 has been described as beingcone-shaped, enlarged features of any of various other shapes that allowthe spike to pierce the rubber seal 123 of the vial 116, 118 and thenengage the inner surface of the seal 123 can be used. In certainimplementations, for example, as shown in FIG. 11, a central spike 336of a drug vial spike 320 includes a barb 342 extending from its sidesurface.

As discussed above, circumferential sidewalls of the cup-shaped drugvial spikes 120, 220, 320 help to prevent the central spike 136, 236,336 from being inadvertently contacted prior to its insertion into thevial 116, 118. Other spike protection devices can alternatively oradditionally be used with any of the drug vial spikes described above.In certain implementations, the spikes of the above-described spikeassemblies are provided with protective covers that can be removed priorto loading the drug vials onto the spikes. The covers can help toprevent the spikes from coming into physical contact with objects thatmight contaminate the spikes. For example, the covers can help to ensurethat the user does not accidentally spike himself or herself whileloading the drug vials onto the spikes. The covers can also help toprevent the spikes from puncturing the sterile bags in which the drugadministration fluid line sets, which include the spikes, are providedto the user.

Referring to FIG. 12, one such spike cover 160 is a unitary plasticstructure that includes tubular members 162 extending downward from anelongate structure 164. The tubular members 162 form cavities in whichthe multiple central spikes 136 of the drug vial spikes 120 of the drugadministration fluid line set 107 are disposed prior to their insertioninto the vials 116, 118. The cavities are sized and shaped so that theportions of the tubular members 162 forming those cavities grip theirassociated spikes 136 with sufficient force to prevent the cover 160from falling off or being inadvertently knocked off the spikes 136 priorto loading the vials 116, 118 onto the spikes 136, while allowing theoperator of the system to manually remove the cover 160 from the spikes136 at the desired time. A lip or overhang extends around thecircumference of the elongate member 164 of the cover 160 to allow theoperator to easily grasp the cover 160 for removal from the spikes 136.As an alternative to or in addition to this lip or overhang, the cover160 can include a tab extending from one end to allow the user tosequentially peel the cover 160 away from the spikes.

While the drug administration fluid line set 107 has been described asincluding multiple feeder lines 122 that connect to the main drugdelivery line 104 via T-connectors 124 and line segments 126, otherarrangements are possible. In some implementations, for example, thefeeder lines 122 are welded or adhesively bonded to the drug deliveryline 104 in a manner such that drug can be fed directly from the feederlines 122 into the drug delivery line 104. Alternatively, the feederlines 122 and the drug delivery line 104 can be integral with oneanother to achieve the same effect.

FIG. 13 shows a slightly modified drug administration fluid line set 207in which the feeder lines 122 are retained in a spaced apartconfiguration by a frame 166. The frame 166 includes along its bottomedge a manifold 168 that functions in a manner similar to theT-connectors 124 and line segments 126 illustrated above in FIG. 2, twoside support members 170, 172 that extend from the manifold 168, and atop support member 174 that extends between the two side support members170, 172. The side support members 170, 172 are attached (e.g.,thermally bonded, adhesively bonded, or mechanically attached) at theirbottom and top ends to the manifold 168 and top support member 174,respectively. The feeder lines 122 similarly extend between and areattached (e.g., thermally bonded, adhesively bonded, or mechanicallyattached) to the manifold 168 and top support member 174.

The manifold 168, side support members 170, 172, and top support member174 are typically formed of one or more materials that are more rigidthan the material or materials from which the feeder lines 122 are made.In certain implementations, the manifold 168, side support members 170,172, and top support member 174 are formed of polycarbonate or AMS.However, other relatively rigid materials can alternatively oradditionally be used. Due to the construction and materials of the frame166, the frame 166 is sufficiently rigid to maintain its generalrectangular shape, and is thus capable of maintaining the feeder lines122 in substantially fixed positions relative to one another.

Still referring to FIG. 13, the drug vial spikes 120 are secured to thetop support member 174 of the frame 166. The drug vial spikes 120 can,for example, be thermally bonded, adhesively bonded, or mechanicallyattached to the top support member 174. The feeder lines 122 are influid communication with their associated drug vial spike 120 and with acentral passage that extends along the length of the manifold 168. Thus,when the central spikes 136 of the drug vial spikes 120 penetrate therubber seals 123 of the vials 116, 118, drugs can flow through thefeeder lines 122 and into the central passage of the manifold 168. Thedrug delivery line 104 is similarly connected to the manifold 168 and isin fluid communication with the central passage of the manifold 168. Asa result, during use, drugs can travel from the vials 116, 118 to thedrug delivery line 104 and ultimately to the drip chamber 106 of theblood circuit where the drugs mix with the patient's blood.

Because the frame 166 holds the feeder lines 122 in substantially fixedpositions relative to one another, loading of the above-described drugadministration fluid line set 207 is simplified. For example, afterloading one of the feeder lines 122 into its associated components(e.g., air bubble detector 128 and occluder 130) on the drug deliverydevice 130, the remaining feeder lines 122 will be generally alignedwith their associated components of the drug delivery device 103 due tothe rigidity of the frame 166. Thus, the operator can more easily loadthe remaining feeder lines 122 into their associated drug deliverydevice components without having to first identify and untangle thosefeeder lines.

While the drug delivery device 103 described above includes a singledrug pump 132 and multiple occluders 130 that are operated in a mannerto control drug flow from the feeder lines 122 to the drug delivery line104, other arrangements for controlling the drug flow can be used. Incertain implementations, for example, each of the feeder lines 122 canbe connected to (e.g., threaded through) its own associated pump (e.g.,a peristaltic pump). In some such implementations, the drug deliverydevice 103 does not include a pump connected to the drug delivery line104 and does not include separate occluders for occluding the feederlines 122. Rather, the pumps of the drug delivery device, which areconnected to the feeder lines 122, can be individually operated toselectively draw the drug from its associated vial 116, 118 and toocclude its associated feeder line 122 when the pump is not inoperation.

While methods of using the drug delivery device 103 have described inwhich the drug vials 116, 118 are manually pressed onto the centralspikes 136, 236, 336 of the drug vial spikes 120, 220, 320 so that thecentral spikes 136, 236, 336 pierce the rubber seals 123 of the vials116, 118, the drug delivery device 103 can alternatively or additionallybe equipped with one or more moveable drug vial holders so that the drugvials 116, 118 can be automatically loaded onto the drug vial spikes120, 220, 320. The drug delivery device 103 can, for example, includevial holders that are moveable relative to the drug vial spikes 120,220, 320 such that the vial holders and the vials 116, 118 containedtherein can be moved (e.g., moved downward) relative to the drug vialspikes 120, 220, 320 causing the central spikes 136, 236, 336 to piercethe rubber seals 123 of the vials 116, 118. In certain implementations,the vial holders are configured to be moved manually. The vial holderscan, for example, be connected to a mechanism that permits a user tosimultaneously spike all of the vials 116, 118 (e.g., by manipulating alever of the mechanism). Movement of the vial holders can alternativelyor additionally be automated. The mechanism for moving the vial holdersrelative to the drug vial spikes 120, 220, 320 can, for example, beconnected to one or more motors that can be operated to move the vialholders and vials 116, 118 therein relative to the drug vial spikes 120,220, 320.

Similarly, while the drug delivery system 102 has been described asincluding drug vial spikes 120, 220, 320 that are configured to causethe vials 116, 118 to be forced in the upward direction after the vials116, 118 are loaded onto the drug vial spikes 120, 220, 320 and/or asincluding pointed projections that form dents in the caps 119 of thevials 116, 118 in order to inhibit the rubber seals 123 of the drugvials from bulging inwardly into the vials 116, 118 during the spikingprocess, other mechanisms for inhibiting inward bulging of the rubberseals of drug vials can be used. The drug delivery device can, forexample, include vial holders that have top and bottom members that areconfigured to hold a vial therebetween and that are moveable relative toone another such that the vial can be compressed between the top andbottom members. The rubber seal positioned between the neck portion andcap of the vial is compressed as the top and bottom members are movedtoward one another. It has been found that a sufficient compressiveforce can be applied to the rubber seal using this technique tosubstantially prevent the rubber seal from bulging inwardly into thebody of the vial when the rubber seal is pierced by its associatedspike. In certain implementations, the drug delivery device 103 isequipped with vial holders that are configured to move relative toassociated drug vial spikes and include top and bottom members that aremoveable relative to one another to allow the vials 116, 118 to becompressed therebetween. Such vial holders can be operated in twostages. During the first stage, the top and bottom members of the vialholders are moved together to compress the vials 116, 118 therebetween,and during the second stage, the vial holders are moved relative to thespikes to cause the associated drug vial spikes to pierce the rubberseals 123 of the vials 116, 118.

While the drug delivery device 103 has been described as including acontrol unit that can control various functions of the drug deliverydevice 103, in certain implementations, the drug delivery device isinstead connected to a control unit of the hemodialysis machine, whichis programmed to cause the drug delivery device to operate in the mannerdescribed above. Similarly, while the drug delivery device 103 has beendescribed as including a user interface that can be used to enterinformation, such as prescribed drug dosages, into the drug deliverydevice 103, in certain implementations, the drug delivery deviceincludes no such user interface and instead a user interface of thehemodialysis machine to which it is attached is used to enter theinformation required for operating the drug delivery device.

FIG. 14 illustrates another hemodialysis system 700 that includes a drugdelivery system 702 for delivering drugs, such as Epogen® and Venofer®,to the blood circuit connected to a hemodialysis machine 701. The drugdelivery system 702 includes a modular drug delivery device 703 that isattached to and exposed on the face of the hemodialysis machine 701 anda disposable drug administration fluid line set (also referred to hereinas a drug administration fluid line cassette) 707 that is connected tothe drug delivery device 703. The disposable drug administration fluidline cassette 707, which is similar to the drug administration fluidline set described with respect to FIG. 13, is disposed in a cassettecompartment formed between a door 704 and an inner face of the drugdelivery device 703 and is used to transport the drugs from the drugvials 116, 118 to the drip chamber 106 of the blood circuit connected toa hemodialysis machine 701.

FIG. 15 illustrates the drug administration fluid line cassette 707 withits protective spike cover 760 removed from its spikes 736. As shown,the feeder lines 122 are retained in a spaced apart configuration by theframe 166 of the cassette 707. In addition to the frame 166, whichincludes the manifold 168, the two side support members 170, 172, andthe top support member 174, the cassette 707 includes a crossbar 776that extends between the two side support members 170, 172. The crossbar776 includes recessed regions 778 into which the feeder lines 122 arereceived and retained. In addition, hexagonal holes 780 are provided inthe front surface of the cassette 707 (i.e., the surface of the cassette707 that contacts the inner surface of the door 704 of the drug deliverydevice 703 when the cassette 707 is loaded in the cassette compartmentof the drug delivery device 703). As described below, these holes 780mate with hexagonal projections 706 extending from the inner surface ofthe door 704 to secure the cassette 707 to the door 704 during use andto help ensure that only appropriate cassettes (e.g., cassettes intendedfor use with the drug delivery device 703 by the drug delivery devicemanufacturer) are used with the drug delivery device 703.

Still referring to FIG. 15, the spikes 736 are attached (e.g., thermallybonded, adhesively bonded, and/or mechanically attached) to and extendupward from the top support member 174 of the cassette 707. The spikes736 can have a construction similar to the construction of the centralspikes 136 described above with respect to the drug vial spikes 120. Forexample, each of the spikes 736 can include a central channel thatextends along the length of the spike and two openings (e.g., channelsor slots) along the outer surface of the spike that lead to the centralchannel. The central channel of each spike is aligned with and fluidlyconnected to a vertical passage extending through the top support member174.

The feeder lines 122 are in fluid communication with their associatedspikes 736 via the vertical passages extending through the top supportmember 174. The feeder lines are also in fluid communication (viaopenings in the top surface of the manifold 168) with the centralpassage that extends through the manifold 168. The drug delivery line104 is similarly connected to the manifold 168 and is in fluidcommunication with the central passage of the manifold 168. Thus, whenthe spikes 736 penetrate the rubber seals 123 of the vials 116, 118during use, drug can flow through the feeder lines 122, the manifold168, the drug delivery line 104, and into the drip chamber 106.

The manifold 168, the side support members 170, 172, the top supportmember 174, and the crossbar 776 are typically formed of one or morematerials that are more rigid than the material or materials from whichthe feeder lines 122 are made. Examples of such relatively rigidmaterials include polycarbonate and AMS. However, other relatively rigidmaterials can alternatively or additionally be used. Due to theconstruction and materials of the frame 166 and cross bar 776 of thecassette 707, the feeder lines 122 are held in substantially fixedpositions relative to one another. As a result of this configuration,loading of the drug administration fluid line cassette 707 into thecassette compartment of the drug delivery device 703 is simplified.

Still referring to FIG. 15, the spike cover 760 includes multipletubular members 762 that extend from a top structure 764. The varioustubular members 762 are interconnected by wall segments 765 that providethe spike cover 760 with added rigidity. The spike cover 760 is used inthe same manner as the spike cover 160 described above with respect toFIG. 12. The spike cover 760 is removed form the spikes 736 of thecassette 707 prior to loading the vials 116, 118 onto the spikes 736.

Referring again to FIG. 14, which illustrates the cassette 707 in thecassette compartment of the drug delivery device 703, the spikes 736 ofthe cassette 707 have been inserted into the vials 116 and 118, whichare retained in vial holders 708 and 710, respectively. Peristalticpumps 732 extend from the inner face of the drug delivery device 703 andalign with the feeder lines 122 (between the cross bar 776 and themanifold 168 of the cassette 707) such that when one of the pumps 732 isoperated, the drug is drawn from the vial 116, 118 associated with thatpump and delivered via the feeder lines 122, the manifold 168, and thedrug delivery line 104 to the drip chamber 106 of the blood circuit.

FIG. 16 illustrates the drug delivery device 703 with the door 704opened and the drug administration fluid line cassette 707 removed. Asshown, the inner surface of the door 704 includes a recessed region 712that is configured to receive the rigid frame 166 of the cassette 707and elongate slots 714 that are configured to receive the feeder lines122 of the cassette 707 without substantially deforming the feeder lines122. In certain implementations, the recessed region 712 and slots 714are sized so that the frame 166 and feeder lines 122 of the cassette 707can be snapped into the recessed region 712 and slots 714, respectively,and thus releasably secured to the door 704. The inner surface of thedoor 704 also includes the hexagonal projections 706 that are configuredfit into the hexagonal holes 780 formed in the cassette 707 when thecassette 707 is loaded into the door 704. The hexagonal projections 706can be sized and shaped to create a snap fit or a snug press fit thatsecures the drug administration fluid line cassette 707 to the door 704.

In addition, the inner surface of the door 704 includes spring-loadedmembers 716 that define recesses or raceways 718 that receive rollermembers of the peristaltic pumps 732 of the drug delivery device 703when the door 704 is closed. Springs are connected to top and bottomregions of each member 716 and to an internal fixed member in the door704 to allow the members 716 to flex in response to contact with therollers of the peristaltic pumps 732 or in response to contact with thefeeder lines 122 positioned between the members 716 and the rollers ofthe peristaltic pumps 732.

Still referring to FIG. 16, the peristaltic pumps 732 are positioned ina spaced configuration across the face of the drug delivery device 703.Each peristaltic pump 732 includes a rotatable frame 730 and multiplerollers 733 rotatably positioned around the circumference of the frame.The peristaltic pumps 732 are configured to rotate about an axis thatextends in a direction that is substantially parallel to the face of thedrug delivery device 703. When the cassette 707 is positioned in thecassette compartment between the inner face of the drug delivery device703 and the closed door 704, the feeder lines 122 align with the pumps732 and are thus pressed into the raceways 718 of the spring-loadedmembers 716 in the door 704. The spring force provided by the springs ofthe spring-loaded members 716 help to take up tolerance between theraceways 718 and the rollers 733 and thus help to ensure that a fixedcompression force is applied to the feeder lines positioned between theraceways 718 and the rollers 733. During operation of the pumps 732, therollers are rotated from top to bottom (in the view show in FIG. 16) andthus force pillows of fluid downward through the associated feeder lines122. This draws a vacuum on the associated vial 116, 118 causing drug tobe drawn into the feeder lines 122 from the vials 116, 118.

The spacing of the rollers 733 about the circumference of the rotatableframe 730 of the peristaltic pumps 732 is selected so that at least oneof the rollers 733 is positioned in the raceway 718 of the associatedspring-loaded member 716 when the door 704 of the drug delivery device703 is closed. This helps to ensure that the feeder lines 122 positionedbetween the pumps 732 and the raceways 718 are always occluded in atleast one location and thus helps to prevent the drugs from passingthrough the feeder lines 122 to the manifold 168 when the pumps 732 arenot in operation.

In certain implementations, the springs that connect the members 716 tothe internal structure of the door 704 can be adjusted or replaced tochange the force applied to the rollers of the peristaltic pumps 732during operation of the pumps 732. The relatively easy accessibility tothe door 704 of the drug delivery device 703 can facilitate thisprocess. In addition, spring loading the raceway members 716 rather thanthe peristaltic pumps 732 themselves can simplify the design of, andthus reduce the manufacturing cost of, the drug delivery device 703.

FIG. 17 shows drive mechanisms 720 of the peristaltic pumps 732. Each ofthe drive mechanisms includes an electric motor 722 having an outputshaft 724. A worm gear 726 is positioned on the end of the output shaft724 and is configured to engage a gear 729 that is secured to the frame730 of the associated peristaltic pump 732. To drive the peristalticpump 732, electrical power is supplied to the motor 722, causing theoutput shaft 724 and the worm gear 726 attached thereto to rotate. Theengagement of the worm gear 726 with the gear 729 of the frame 730causes the frame 730 and the rollers 733 attached thereto to rotateabout a fixed support rod 734. Because each peristaltic pump 732 has itsown drive mechanism 720, the peristaltic pumps 732 can be independentlyoperated such that drug can be drawn from one drug vial 116, 118 at atime. The speed of the peristaltic pumps 732, and thus the rate at whichthe drugs are withdrawn from the vials 116, 118, can be altered byaltering the power or voltage supplied to the motors 722.

Referring again to FIG. 16, bubble detectors 128, which were describedin greater detail above, are also arranged in a spaced configurationacross the inner face of the drug delivery device 703 above theperistaltic pumps 732. As discussed above, the bubble detectors 128 arecapable of detecting air bubbles within the feeder lines 122 and canthus be used to determine whether the drug vial 116, 118 associated witha particular feeder line 122 is empty during treatment.

The drug vial holder 708 of the modular drug delivery device 703 isconfigured to hold a single Venofer® vial 116, and the drug vial holder710 is configured to hold up to three Epogen® vials 118. The drug vialholder 708 includes a top member 738 and a bottom member 740 that canretain the single Venofer® vial 116 therebetween. The bottom member 740has a top surface on which the cap of the inverted Venofer® vial 116 canrest. In certain implementations, the bottom member 740 includes arecess that is sized and shaped to receive the cap 119 (or a portion ofthe cap 119) of the vial 116. This recess can help to ensure that thevial 116 is properly positioned in the vial holder 708. The bottommember 740 of the drug vial holder 708 also defines a through openingthat allows an associated spike 736 of the drug administration fluidline cassette 707 to pass through the bottom member 740 and pierce therubber seal 123 of the Venofer® vial 116 during use.

The top and bottom members 738, 740 of the drug vial holder 708 aremoveable relative to one another such that a drug vial can be compressedtherebetween. In addition, the drug vial holder 708 as a whole ismoveable in the vertical direction relative to the inner face of thedrug delivery device 703 and relative to an associated spike 736 of thedrug administration fluid line cassette 707 when the cassette 707 isdisposed in the cassette compartment of the drug delivery device 703. Asa result, when the cassette 707 is disposed in the cassette compartment,the top and bottom members 738, 740 of the drug vial holder 708 can bemoved in unison along with the Venofer® vial 116 to cause the associatedspike 736 of the cassette 707 to pierce the rubber seal 123 of the vial116.

The drug vial holder 710, which holds the Epogen® vials 118 during use,is similar to the drug vial holder 708 described above. In particular,this drug vial holder 710 also includes top and bottom members 742, 744between which three Epogen® vials 118 can be held, and the bottom member744 defines three openings through which spikes 736 of the cassette 707can pass to pierce the rubber seals 123 of the vials 118. In someimplementations, the upper surface of the bottom member 744 definesrecesses that receive the caps 119 of the Epogen® vials 118 and help toensure that the vials 118 are properly positioned in the vial holder710. These recesses can, for example, help to ensure that the vials 118are aligned with the openings in the bottom member 744 to allow thespikes 736 of the cassette 707 to pierce the rubber seals 123 of thevials 118.

FIG. 18 shows drive mechanisms 746 and 747 that can be used to operatethe drug vial holders 710 and 708, respectively. The drive mechanism 746can move the top and bottom members 742, 744 of the drug vial holder 710in order to clamp or compress the rubber seals 123 of the Epogen® vials118 between their caps 119 and neck portions 121 and to cause the spikes736 of the drug administration fluid line cassette 707 to pierce therubber seals 123 of the vials 118. Similarly, the drive mechanism 748can move the top and bottom members 738, 740 of the drug vial holder 708in order to clamp or compress the rubber seal 123 of the Venofer® vial118 between its cap 119 and neck portion 121 and to cause one of thespikes 736 of the cassette 707 to pierce the rubber seal 123 of the vial118. The drive mechanisms 746, 747 are positioned within the housing ofthe hemodialysis machine 701 behind the inner face of the drug deliverydevice 703. Thus, the drive mechanisms 746, 747 would not typically bevisible to the user. Because the drive mechanisms 746, 747 havegenerally the same structure and function, we only describe thestructure and function of the drive mechanism 746 in detail.

Still referring to FIG. 18, the drive mechanism 746 includes a driveshaft 748 that is rotatably disposed within bores in top and bottomsupports 749, 750 that are fixed to the face or housing of the drugdelivery device 703. The top and bottom end regions of the drive shaft748 can, for example, be connected to the top and bottom supports 749,750 by bearings (e.g., ball bearings) that allow the drive shaft 748 torotate with respect to the top and bottom supports 749, 750. At least atop region of the drive shaft 748 is threaded. A vertical support wall751 is fixed at its top and bottom ends to the top support 749 andbottom support 750, respectively. The vertical support wall 751 is fixedrelative to the face or housing of the drug delivery device 703.

Top and bottom member extensions 752 and 753 extend from the rear ofeach of the top and bottom members 742 and 744, respectively, of thedrug vial holder 710, near right and left end regions of those top andbottom members 742, 744. The top and bottom member extensions 752, 753pass through vertical slots 754 in the face of the drug delivery device703 and are thus free to move up and down with respect to the face ofthe drug delivery device 703. As a result, the top and bottom members742, 744 of the drug vial holder 710 are allowed to move up and downwith respect to the face of the drug delivery device 703. A cross bar755 extends horizontally between the two top member extensions 752 andis attached in opposite end regions to those extensions 752. Similarly,a cross bar 756 extends horizontally between the two bottom memberextensions 753 and is attached in opposite end regions to thoseextensions 753. Each of the cross bars 755, 756 includes a hole throughwhich the drive shaft 748 passes. The holes typically have largerdiameters than the outer diameter of the drive shaft 748 such that thecross bars 755, 756 can move vertically along the drive shaft 748without contacting the drive shaft 748.

The inside surfaces (i.e., the surfaces facing the drive shaft 748) ofthe top and bottom member extensions 752, 753 include vertical channelsthat are configured to receive linear guides 757 that extend fromopposite side surfaces of the vertical support wall 751. Thisarrangement helps to ensure that the two top member extensions 752remain substantially level with one another and remain substantiallyperpendicular to the face of the drug delivery device 703 as thoseextensions move up and down along the slots 754. The same effect isachieved with respect to the two bottom member extensions 753. Thelinear guides 757 can be formed of a low-friction material, such aspolyoxymethylene (marketed under the tradename Delrin and available fromDupont of Wilmington, Del.), in order to reduce the resistance appliedto the sliding top and bottom member extensions 752, 753.

Still referring to FIG. 18, a drive member (e.g., ball screw) 758 isattached to the top cross bar 755 in a manner such that the drive member758 is substantially prevented from moving vertically or rotationallyrelative to the cross bar 755. The drive member 758 includes a centralpassage with threads that are configured to engage threads of the topthreaded region of the drive shaft 748. The engagement of these threadsin combination with the substantial inability of the drive member 758 torotate with respect to the drive shaft 748 causes the drive member 758to move vertically along the drive shaft 748 as the drive shaft 748 isrotated. Whether the drive member 758 moves up or down along the driveshaft 748 depends on the direction of rotation of the drive shaft 748.Because the drive member 758 is fixed to the cross bar 755, which isfixed to the top member extensions 752, which are attached to the topmember 742 of the vial holder 710, rotation of the drive shaft 748 canmove the top member 742 of the vial holder 710 up and down with respectto the face of the drug delivery device 703.

As discussed above, both the top member extensions 752 and the bottommember extensions 753 ride along the linear guides 757. The top andbottom member extensions 752, 753 are positioned such that, when thevials 118 are disposed in the vial holder 710, the top and bottom memberextensions 752, 753 will not contact one another even as the top memberextensions 752 are moved downward. At some point, as the top memberextensions 752 move downward relative to the bottom member extensions753, the top member 742 of the drug vial holder 710 will contact thevials 118 and the vials 118 will be compressed between the top andbottom members 742, 744 of the drug vial holder 710.

A spring 759 is disposed between and attached to the bottom cross bar756 and the bottom support 750. As the top member 742 of the drug vialholder 710 is moved downward toward the bottom member 744 and contactsthe bottom surfaces (facing up) of the inverted vials 118, a force isapplied to the spring 759. The spring force coefficient is selected sothat this force does not initially permit the bottom member 744 of thedrug vial holder 710 to move downward. Instead, the downward movement ofthe top member 742 causes the rubber seals 123 of the vials 118 to becompressed between the caps 119 and neck portions 121 of the vials 118.To achieve this effect, the spring 759 has a spring force coefficientthat is greater than a collective spring force coefficient of the rubberseals 123 of the vials 118. In certain implementations, the spring isconfigured to provide a resistance force of about 1 pound to about 20pounds (e.g., about 1 pound to about 10 pounds, about 1 pound to about 5pounds, about 5 pounds to about 10 pounds). The compression of therubber seals 123 between the caps 119 and neck portions 121 of the vials118 inhibits movement of the rubber seal 123 relative to the caps 119and neck portions 121 of the vials 118. This can advantageously inhibitor prevent the rubber seals 123 from bulging into the vials as thespikes 736 of the drug administration fluid line cassette 707 pierce therubber seals 123. This spiking technique is described in greater detailbelow.

A gear 761 is attached to a bottom end region of the drive shaft 748.This drive shaft gear 761 is engaged with a gear 763 that is connectedto an output shaft of a motor (e.g., an electric motor) 766. When themotor 766 is operated, the output shaft and the gear 763 connectedthereto rotate. This causes the drive shaft gear 761 and the drive shaft748 to rotate. As a result, operation of the motor 766 can be used tomove the top member 742 of the drug vial holder 710 relative to thebottom member 744 of the drug vial holder 710 and, after compressing thevials 118 between the top and bottom members 742, 744, to move the topand bottom members 742, 744 and the vials 118 therebetween in unisonrelative to the spikes 736 of the drug administration fluid linecassette 707, which is substantially fixed relative to the face of thedrug delivery device 703.

Referring again to FIGS. 14-16, the drug vial holders 708, 710 of thedrug delivery device 703 can be equipped with any of the various typesof sensors described above for sensing the presence of a vial,identifying the type drug vial installed, detecting the size of the drugvials, and/or detecting the mass of the drug vials.

The drug delivery device 703 also includes a control unit similar to thecontrol unit described above with respect to the drug delivery device103. The control unit can power and control the various components ofthe drug delivery device 703, including the bubble detectors 128, thedrug pumps 732, and the various sensors. For example, the control unitcan control the pumps 732 to ensure that only one of the pumps 732 is inoperation at a time. This helps to ensure that drug is pulled from onlyone of the vials 116, 118 at a time during treatment. Upon determiningthat the prescribed volume of the drug has been delivered (based onmonitoring the operation of the pumps 732), the control unit can turnoff the pump 732 associated with that drug vial 116, 118 and turn on thepump 732 associated with the drug vial 116, 118 containing the next drugto be delivered. In addition, after the full contents of a vial havebeen evacuated, air will be sucked into the feeder line 122 associatedwith that vial and will be detected by the bubble detector 128. Inresponse, the control unit can turn off the pump 732 associated with theempty vial and turn on the pump 732 associated with the vial containingthe next drug to be delivered.

In addition, upon receiving signals from the drug vial ID sensors thatdo not match the inputted treatment information, an alarm (e.g., anaudible and/or visual alarm) can be activated. Alternatively oradditionally, the drug delivery device 103 can be configured so thattreatment cannot be initiated until the sensors detect the correctcombination of vials.

Like the drug delivery device 103, the drug delivery device 703 isconfigured to sense if the blood pump 108 of the dialysis machine 701 isrunning and to pause drug delivery if the blood pump 108 is stopped.This technique prevents ‘pooling’ of the delivered drug in the dripchamber 106.

Still referring to FIGS. 14-16, a method of using the hemodialysissystem 700 to perform hemodialysis on a patient will now be described.Prior to beginning the hemodialysis treatment, the various lines andpassages that make up the blood circuit and dialysate circuit of thehemodialysis machine 701 are primed, and then the patient lines 105 areconnected to the patient. The hemodialysis treatment is then initiatedby activating the blood pump 108 and dialysate pump of the dialysismachine 701 to circulate blood and dialysate through the blood anddialysate circuits, respectively.

After initiating the hemodialysis treatment, the operator of thehemodialysis system 700 (e.g., the physician, nurse, medical assistant,or patient) determines the prescribed Epogen® dose and then consults adosing schedule for the different vial combinations that can be used todeliver the prescribed Epogen® dose. The operator then selects one ofthe Epogen® vial combinations provided based on the operator'spreference and loads the selected Epogen® vials into the drug vialholders. The operator also loads a vial of Venofer® into one of the drugvial holders.

The operator of the system then connects the disposable drugadministration fluid line cassette 707 to the inner surface of the door704 by inserting the frame 166 and feeder lines 122 into theircorresponding recessed regions 712 and slots 714. As a result of this,the hexagonal shaped projections 706 that extend from the inner surfaceof the door 704 slide into the matching holes 780 formed in the frame166 of the drug administration fluid line cassette 707. The matingengagement of the hexagonal shaped projections 706 and openings 780,along with the snap fit of the cassette frame 166 and feeder lines 122into their corresponding recessed regions 712 and slots 714, helpsensure that the cassette 707 remains securely fixed to the door 704. Inaddition, the unique hexagonal shape of the projections 706 and openings780 can help to ensure that only drug administration fluid linecassettes intended for use with the drug delivery device 703 can beused. For example, drug administration fluid line cassettes that do notinclude holes capable of receiving the hexagonal projections 706 of thedoor 704 could not be properly secured to the door 704. This wouldindicate to the operator that an incorrect cassette was loaded into thecassette compartment of the drug delivery device 703 and, in many cases,will prevent the door 704 from shutting and thus prevent the drugdelivery device 703 from being operated with that cassette.

After loading the drug administration fluid line cassette 707 onto thedoor 704, the operator closes the door 704 and secures a latch 767 tohold the door 704 in the closed position. Because the cassette 707 issecurely fastened to the door 704 in a desired position, the feederlines 122 align with their associated pumps 732 and bubble detectors 128when the door 704 is closed. Thus, as the door 704 is closed, theprotruding peristaltic pumps 732 press the feeder lines 122 into theraceways 718 formed along the inner surface of the door 704, and theinner surface of the door 704 presses the feeder lines 122 intoengagement with the bubble detectors 128. With the door 704 in theclosed position, the spikes 736 of the cassette 707 rest directly belowthe holes formed in the bottom members 740, 744 of the vial holder 708,710.

The prescribed dosages of Venofer® and Epogen® are then entered into thedrug delivery device 703 using the user interface 734 of thehemodialysis machine 701 with which the control unit of the drugdelivery device 703 is in communication. Alternatively or additionally,the prescribed dosage of Venofer® and Epogen® can be electronicallytransmitted to the control unit of the drug delivery device 703 from adatabase or website accessible by the patient's prescribing physician.The operator, after reviewing the prescribed dosage entered into ortransmitted to the machine, confirms that the prescribed dosage iscorrect by pressing a button (e.g., an “Accept” or “Confirm” button) onthe user interface 734 of the hemodialysis machine 701, which initiatesthe spiking and priming process.

Referring briefly again to FIG. 18, the vial spiking process begins byactivating the motors 766 of the drive mechanisms 746, 747 connected tothe vial holders 708, 710, which first causes the vial holders 708, 710to compress the rubber seals 123 of the vials 116, 118 between the caps119 and necks 121 of the vials 116, 118, and then, upon continuedoperation of the drive mechanisms 746, 747, causes the vials 116, 118 tomove sufficiently downward so that the spikes 736 of the cassette 707pierce the rubber seals 123 of the vials 116, 118. In particular,operation of the motors 766 of the drive mechanisms 746, 747 causes thetop members 738, 742 of the drug vial holders 708, 710 to move downwardand squeeze the vials 116, 118 between the top members 738, 742 andbottom members 740, 744 of the drug vial holders 708, 710. Before thesubsequent step of causing the top members 738, 742 and bottom members740, 744 of the drug vial holders 708, 710 to move downward in unison sothat the spikes 736 of the drug administration fluid line cassette 707pierce the rubber seals 123 of the vials 116, 118, the rubber seals 123are compressed to a sufficient degree to inhibit movement of the rubberseals 123 relative to the caps 119 and neck portions 121 of the vials116, 118. The compression of the rubber seals 123 results from theinitial resistance to downward force of the bottom members 740, 744 ofthe drug vial holders 708, 710 as the downward moving top members 738,742 contact the vials 116, 118 and squeeze the vials between the top andbottom members. This resistance to downward force is provided by thesprings 759 disposed between the bottom cross bars 756 and the bottomsupports 750. After the rubber seals 123 are sufficiently compressed,the motors 766 of the drive mechanisms 746, 747 continue to run and theforce applied to the bottom members 740, 744 of the drug vial holders708, 710, and thus to the bottom member extensions 753, rises to asufficient level to cause the springs 759 to collapse, which results indownward movement of the bottom members 740, 744 along with the topmembers 738, 742 and the vials 116, 118. The motors 766 continue to rununtil the vial holders 708, 710 are moved downward a sufficient distanceto cause the spikes 736 to pass through the openings in the bottommembers 740, 744 of the drug vial holders 708, 710 and pierce the rubberseals 123 of the vials 116, 118. Because the rubber seals 123 are heldin a compressed state while they are pierced by the spikes 736, bulgingof the rubber seals 123 into the neck portion 121 of the vials 116, 118can be inhibited or prevented.

In certain implementations, to counteract any inward bulging of therubber seals 123 that might have occurred during the spiking process,the motors 766 are operated in the reverse direction for a brief periodof time after the spikes 736 have been fully inserted into the vials116, 118 (e.g., after the bottom members 740, 744 of the drug vialholders 708, 710 or the caps 119 of the drug vials 116, 118 havecontacted the bases or support members from which the spikes 136 extend)in order to move the vial holders 708, 710 up slightly. As the vialholders 708, 710 move upward, friction between the spikes 736 and therubbers seals 123 of the vials 116, 118 causes a downward force to beapplied to the rubber seals 123. Depending on the period of time forwhich the motors 766 are operated in the reverse direction, the rubberseals 123 can be returned to their neural resting position (i.e., notbulged inward and not bulged outward), or the rubber seals 123 can becaused to bulge slightly outward from the vials 116, 118. Eitherconfiguration will help to ensure that the drugs are fully evacuatedfrom the vials during the drug delivery process.

After spiking the vials 116, 118, the feeder lines 122 of the drugadministration fluid line cassette 707 are primed by activating thepumps 732, either sequentially or simultaneously, which causes a portionof the drug to be drawn from each of the vials 116, 118. During thepriming process, each pump 732 remains on until the drug from itsassociated vial 116, 118 is detected by the bubble detector 128, atwhich point the pump 732 is stopped and pinches off or occludes thatfeeder line 122. If the drug is not detected by one of the bubbledetectors 128, an alarm can be activated prompting the operator toreplace or adjust the drug administration fluid line cassette 707 andrepeat the priming process.

After priming the feeder lines 122, Venofer® is delivered from theVenofer® vial 116 to the drip chamber 106 by activating the pump 732associated with the Venofer® vial 116 (while leaving all of the otherpumps off). Upon determining that the prescribed dosage of Venofer® hasbeen delivered to the drip chamber 106, the control unit causes the pump732 associated with the Venofer® feeder line to be turned off.

The pump associated with the first Epogen® vial 118 (i.e., the Epogen®vial directly to the right of the Venofer® vial 116) is then activatedsuch that Epogen® is delivered to the drip chamber 106. When the bubbledetector 128 detects air in the feeder line 122, a signal is sent to thecontrol unit, indicating that the first Epogen® vial 118 is empty. Thecontrol system then sends a signal causing the pump associated with thefirst Epogen® vial 118 to be turned off after assuring that anadditional known volume is pumped so that the Epogen® in the linedownstream of the bubble detector 128 is flushed down to a segment wherethe delivery of drug from the next vial can push that Epogen® remainingin the line to the drip chamber 106. In particular, the control unitensures that the additional pumped volume is sufficient to push theEpogen® past the pump 732 and into the passage of the manifold 168 suchthat the next volume of drug delivered will push the Epogen® to the dripchamber 106. The control unit also sends a signal to activate the pump732 associated with the second Epogen® vial 118 (i.e., the Epogen® vialdirectly to the right of the first Epogen® vial). The Epogen® deliveryprocess described above is then repeated for the second and thirdEpogen® vials.

After delivering the desired amounts of Venofer® and Epogen® to the dripchamber 106, the drug delivery device 703 is deactivated and the drugadministration fluid line cassette 707 and vials 116, 118 are removedfrom the drug delivery device 703 and discarded.

In some implementations, an air bubble is pulled into the passage of themanifold 168 via the feeder line 122 and delivered to the drip chamber106 when transitioning from one drug vial to the next. This technique,as described above, can help to clear any remaining medicament from thepreviously used vial out of the manifold passage and drug delivery line104 to help ensure that all of the drug evacuated from the vial isdelivered to the patient and to reduce (e.g., eliminate) mixing of twodistinct drugs both of which are delivered to the drip chamber 106 viathe manifold passage and drug delivery line 104.

In certain implementations, the operating speed of each of the pumps 732is gradually increased as the quantity of drug in the vial from whichthe drug is being withdrawn decreases. As the quantity of drug in thevial decreases, a slight vacuum is produced in the vial. This vacuum canresult in a decreased flow rate of the drug from the vial if the pumpspeed remains constant. Thus, gradually increasing the pump speed as thedrug is drawn from the vial can help to maintain a substantiallyconstant flow rate of the drug from the vial throughout the drugdelivery process.

While the raceway members 716 that are exposed on the inner surface ofthe door 704 of the drug delivery device 703 and receive the rollers 733of the peristaltic pumps 732 have been described as being connected tothe door 704 via springs located at the top and bottom regions of theraceway members 716, alternative configurations are possible. In someimplementations, for example, only a single spring is used to connecteach raceway member 716 to the door 704. The single spring can, forexample, be connected to a mid-region of the raceway member.

While the door 704 of the drug delivery device 703 has been described asincluding hexagonal projections 706 that mate with hexagonal holes 780formed in the cassette 707, the reverse configuration is also possible.For example, the cassette 707 can be provided with hexagonal projectionsand the door 704 of the drug delivery device 703 can include hexagonalholes that mate with those projection. Similarly, as an alternative toincluding these mating features on the inner surface of the door 704 andthe front surface of the cassette 707, the mating features can beprovided on the inner face of the drug delivery device 703 and the rearsurface of the cassette 707. Also, as an alternative to hexagonal holesand projections, holes and projections of various other shapes, such aspentagons, octagons, stars, logos, etc., can be used. In certainimplementations, the mating holes and projections are irregularly shapedto further ensure that only cassettes intended for use with the drugdelivery device can be properly disposed in the cassette compartment ofthe drug delivery device.

While the spikes 736 of the drug administration fluid line cassette 707have been illustrated as having sharp, tapered ends, the spikes canalternatively be shaped similar to those spikes 236, 336 described abovewith respect to FIGS. 10 and 11.

While the top members 738, 742 of the drug vial holders 708, 710described above are configured to contact the upward facing bottomsurfaces of the inverted drug vials 116, 118, the top members can beconfigured to contact other portions of the vials. In someimplementations, for example, the drug vial holders include top membersin the form of clamps that grasp the neck portions 121 of the vials 116,118 during use. The clamp mechanisms, when clamping the neck portions121 of the vials 116, 118, can be moved in the downward direction towardthe bottom members 740, 744 such that the rubber seals 123 of the vials116, 118 are compressed between the caps 119 and neck portions 121 ofthe vials 116, 118. While the bodies of drug vials come in a variety ofshapes and sizes, most drug vials have similarly sized and shaped capsand neck portions. Thus, this arrangement can advantageously allow thedrug vial holders to accommodate various differently sized and shapedvials, which can allow the drug delivery device to be used to delivery avariety of different drugs.

While the bottom members 740, 744 of the drug vial holders 708, 710 havebeen described as supporting the caps 119 of the inverted drug vials116, 118, other arrangements are possible. In certain implementations,for example, the bottom members of the drug vial holders includeopenings that are sized to allow the caps 119 of the vials 116, 118 topass therethrough and to prevent the neck portions 121 and/or the bodyportions 125 of the vials 116, 118 from passing therethrough. Each ofthe openings can, for example, be a circular opening that has a diametergreater than the maximum outer diameter of the cap 119 to be insertedtherethrough and less than the maximum outer diameter of the neckportion 121 and/or the body portion 125 of the vial 116, 118. Such vialholders can be used in combination with other mechanisms, such as drugvials spikes 120, that help to prevent the rubber seals of the drugvials from bulging inwardly into the vial when pierced by the spikes.

While the drug vial holder drive mechanisms 746, 747 illustrated in FIG.18 include linear guides 757 that extend from the vertical support wall751 and along which the top member extensions 752 and bottom memberextensions 753 slide during use, the top and bottom member extensionscan alternatively be configured to slide along the side surfaces of thevertical support wall 751 itself.

While each of the drug vial holder drive mechanisms 746, 747 illustratedin FIG. 18 include a single spring 759 that is positioned between thebottom cross bar 756 and the bottom support 750 and surrounds the driveshaft 748, in certain implementations, multiple springs are used toprovide resistance to downward movement of the bottom member of the drugvial holder. As shown in FIG. 19, for example, a drug vial holder drivemechanism 846 includes a spring 859 positioned between bottom memberextensions 853 and a bottom support 850. Each of the bottom memberextensions 853 is L-shaped and includes a vertical member and ahorizontal member. The horizontal member of each bottom memberextensions 853 extends away from the drive shaft 748, toward an outeredge the drug delivery device. This portion, which supports the spring859 is thus positioned nearer the end regions of the bottom member 744of the drug vial holder 710. This arrangement can help to ensure thatsufficient resistance to downward movement is provided to the endregions of the bottom member 744 of the drug vial holder 710 to allowthe rubber seals 123 of the vials 118 located on the opposite ends ofthe drug vial holder 710 to be compressed before the drug vial holder710 as a whole is moved downward toward the spikes 736 of the cassette707. While the drive mechanism 846 may be particularly advantageous fordrug vial holders that are designed to accommodate multiple vials andthus have a relatively wide bottom member, the drive mechanism can beused with drug vial holders that are designed to hold only a singlevial.

Other types of drive mechanisms can also be used to operate the drugvial holders 708, 710 in order to clamp and spike the drug vials 116,118. An example of such a drive mechanism 946 is schematicallyillustrated in FIG. 20. As shown, the drive mechanism 946 includes amotor 902 that is configured to drive an output shaft 904 in an upwarddirection. The output shaft 904 is pivotally connected to a pivot arm906, which is pivotally connected to a housing 908 of the drug deliverydevice via a central pivot 910. As the motor 902 drives the output shaft904 upward, the pivot arm 906 rotates in the clockwise direction aboutthe pivot 910. As a result, a bearing 912 attached to the end of thepivot arm 906 opposite the motor output shaft 904 moves downward. Thebearing 912 is positioned in a cavity 914 of an upper member 916 of adrug vial holder 918, which is shown holding the drug vial 116, 118. Theneck portion of the drug vial 116, 118 is firmly held by a fork or clamp920 of the upper member 916. Thus, as the upper member 916 of the drugvial holder 918 is moved downward, the drug vial 116, 118 retained bythe fork 920 also moves downward.

As the motor 902 continues to drive the output shaft 904 upward, whichcauses the upper member 916 and the drug vial 116, 118 held therein tocontinue to move downward, the cap 119 of the drug vial is forceddownward against a lower member or shoe 922 of the drug vial holder 918.The lower member 922, like the upper member 916 is vertically moveablerelative to the housing of the drug delivery device. A spring 924 isfixed to the housing of the drug delivery device and thus resistsdownward movement of the lower member 922. The spring 924 can, forexample, be configured to withstand a downward force of about 1 pound toabout 20 pounds (e.g., about 1 pound to about 10 pounds, about 1 poundto about 5 pounds, about 5 pounds to about 10 pounds). As the downwardmovement of the lower member 922 is resisted by the spring 924, therubber seal 123 of the drug vial 116, 118 is compressed between the cap119 and neck portion 121 of the drug vial 116, 118.

Further operation of the motor 902 causes the downward force applied tothe lower member 922 to exceed the resistance force of the spring 924.As the spring 924 is compressed, the upper and lower members 916, 922 ofthe drug vial holder 918 and the drug vial holder 116, 118 itself aremoved downward toward a drug vial spike 926. The drug vial spike 926eventually passes through an aperture 928 formed in the lower member 922and pierces the rubber seal 123 of the drug vial 116, 118 such that drugcan be drawn out of the drug vial 116, 118 via the drug vial spike 926.

After the drug has been delivered from the drug vial 116, 118, the motor902 is tuned off and the spring 924 causes the upper and lower members916, 922 of the drug vial holder 918 and the drug vial 116, 118 to moveupward, away from the drug vial spike 926.

While the drug vial holder drive mechanisms described above use one ormore springs to cause the bottom members 740, 744 of the drug vialholders 708, 710 to resist downward movement and thus allow compressionof the rubber seals 123 of the vials 116, 118, other types of devices ormechanisms that are capable of initially resisting vertical movement ofthe bottom member 740, 744 and then allowing downward movement when asufficiently high force is applied to the bottom member 740, 744 can beused. Examples of such devices include opposing polarity magnets,elastomers, or other members that provide a force proportional todisplacement.

As an alternative to or in addition to using a gear arrangement toconnect the output shaft of the motor to the drive shaft of the variousdrug vial holder drive mechanisms described above, other connectiontechniques that allow the motor to rotate the drive shaft can be used.In certain implementations, for example, a pulley is connected to boththe output shaft of the motor and the drive shaft of the drive mechanismin order to allow the motor to rotate the drive shaft.

While the bottom members 740, 744 of the drug vial holders 708, 710 havebeen described as having substantially flat or smooth surfaces on whichthe drug vials 116, 118 rest, those surfaces can alternatively includepointed projections that dent the cap 119 of the vial 116, 118 into therubber seal 123 of the vial 116, 118 when the vial 116, 118 is squeezedbetween the top members 738, 742 and bottom members 740, 744 of the drugvial holders 708, 710. FIG. 21 illustrates drug vial holders 1008, 1010that include such pointed projections. As shown in FIG. 21, each of thedrug vial holders 1008, 1010 includes a bottom member 1040, 1044 withupper surfaces from which three pointed projections 1041, 1045 extend.The pointed projections 1041, 1045 only extend slightly above the uppersurfaces of the bottom members 1040, 1044. In certain implementations,for example, the pointed projections 1041, 1045 extend about 0.010 inchto about 0.030 inch (e.g., about 0.020 inch) above the upper surfaces ofthe bottom members 1040, 1044. As the top members 738, 742 of the drugvial holders 1008, 1010 are moved toward the bottom members 1040, 1044and the vials 116, 118 are squeezed therebetween, the force of thebottom members 1040, 1044 acting upwardly on the caps 119 of the vials116, 118 causes each of the pointed projections 1041, 1045 to dent adiscrete portion of the cap 119 into the rubber seal 123 of the vial116, 118. An illustration of a vial 116, 118 that has been clamped inthis manner is shown in FIG. 22. The discrete portions of the cap 119that protrude into the rubber seal 123 can, in addition to thecompression of the rubber seal 123, help to prevent the rubber seal 123from moving or slipping relative to the cap 119 and neck portion 121 ofthe vial.

While the drive mechanisms of the drug vial holders described aboveinclude motors that cause the top members of the vial holders to moverelative to the bottom member, manually operated drive mechanisms canalternatively or additionally be used. FIG. 23 is a side schematic viewof such a manually operated drive mechanism 1146. The drive mechanism1146 includes lower and upper springs 1102, 1104 disposed along a guideshaft 1106. A collar 1108 is fixed to the guide shaft 1106 below thelower spring 1102, and the bottom end region of the spring 1102 abutsthe collar 1108. A collar 1110 is positioned between the lower and uppersprings 1102, 1104, and a collar 1112 is positioned above the upperspring 1104. Collars 1110, 1112 are moveable along the length of theguide shaft 1106.

An upper member or plate 1118 of a drug vial member 1119 is fixed to thecollar 1112, and a lower member or shoe 1120 of the drug vial holder1119 is fixed to the collar 1110. As a result, as the collars 1110, 1112move relative to the guide shaft 1106, the lower and upper members 1120,1118 of the drug vial holder 1119 similarly move relative to the guideshaft 1106. Much like some of the drug vial holders described above, thelower member 1120 of the drug vial holder 1119 is configured to supportthe cap 119 of the inverted vial 116, 118, and the upper member 1118 isconfigured to move downward relative to the lower member 1120 to clampthe drug vial 1116, 1118 therebetween.

A drug vial spike assembly 1122 is fixed to the collar 1108 via a bar1123. As a result, the drug vial spike assembly 1122 is fixed relativeto the guide shaft 1106. The drug vial spike assembly 1122 includesflexible fingers 1124 that extend upward from a base 1126 and surround acentral spike 1136. The flexible fingers 1124 are configured toreleasably retain the lower member 1120 of the drug vial holder 1119 andthe cap 119 of the drug vial 116, 118 when the lower member 1120 and thedrug vial 116, 118 are moved downward such that the central spike 1136passes through an opening 1121 formed in the lower member 1120 andpierces the rubber seal of the vial 116, 118.

An eccentric cam 1114 having a pivot point 1116 is positioned above thecollar 1112 and is configured to move the collar 1112 along the guideshaft 1106 as the eccentric cam 1114 is rotated by an operator. Theoperator rotates the eccentric cam 1114 by pulling a lever 1117 that isconnected to the eccentric cam 1114. As the cam 1114 rotates, the collar1112 compresses the upper spring 1104, which has a lower resistance thanthe lower spring 1102, and causes the upper member 1118 of the drug vialholder 1119 to move downward. Further compression of the upper spring1104 causes the upper member 1118 to contact the vial 116, 118 and tocompress the vial 116, 118 between the upper and lower members 1118,1120 of the drug vial holder 1119. The lower spring 1102 has a springforce that resists downward movement of the collar 1110 and the lowermember 1120 to an extent to allow the rubber seal of the vial 116, 118to be compressed between the cap 1119 and the neck portion 121 of thevial 116, 118. As the eccentric cam 1114 is rotated further, the spring1102 is compressed and the drug vial holder 1119 and the vial 116, 118are moved downward toward the drug vial spike assembly 1122. Theeccentric cam 1114 is rotated until the central spike 1136 has piercedthe rubber seal of the vial 116, 118, and the lower member 1120 and thevial 116, 118 abut the base 1126 of the drug vial spike assembly 1122.

While the drive mechanism 1146 has been described as being configuredsuch that the collar 1108 is fixed relative to the guide shaft 1106, andthe collars 1110, 1112 are moveable relative to the guide shaft 1106, inother implementations, the collar 1110 is fixed relative to the guideshaft 1106, and the collars 1108, 1112 are moveable relative to theguide shaft 1106. In such implementations, a downward force is appliedto the collar 1112 when the eccentric cam 1114 is rotated, and an upwardforce is applied to the collar 1108 when the eccentric cam 1114 isrotated. Due to the different spring forces of the springs 1102, 1104,the upper spring 1104 is first to compress, causing the upper member ofthe drug vial holder 1119 to move toward the lower member 1120 of thedrug vial holder 1119. After the drug vial 116, 118 has beensufficiently compressed between the upper and lower members 1118, 1120,the lower spring 1102 compressing, allowing the drug vial spike assembly1122 to move upward toward the drug vial 116, 118 such that the centralspike 1136 pierces the rubber seal of the drug vial 116, 118.

As an alternative to or in addition to using the mating projections 706and openings 780 to inhibit or prevent unapproved or incorrect drugadministration fluid line cassettes from being used with the drugdelivery device 703 described above, the drug delivery device 703 caninclude a sensor (e.g., a bar code reader or RFID detector) that canidentify approved or correct drug administration fluid line cassettes(e.g., by reading a bar code reader or RFID tag that identifies thecassette). The sensor can be connected to the control unit, and thecontrol unit can be programmed to prevent operation of the drug deliverydevice unless an approved drug administration fluid line cassette isdetected. These types of sensors can similarly be included in the otherdrug delivery devices described herein.

While the control unit has been described as being part of the drugdelivery device 703, in certain implementations, the control unit is notphysically present in the modular drug delivery device. In suchimplementations, for example, the drug delivery device 703 can beconnected to a control unit located elsewhere in the hemodialysismachine (e.g., the main control unit of the hemodialysis machine).

While the drug administration fluid line sets have been described asbeing provided with unitary, removable covers that protect the spikes ofthose fluid line sets prior to use, other types of covers can be used.In some implementations, a separate cover is attached to each spike ofthe administration fluid line set. As shown in FIG. 24, for example, aspike cover 1200 includes a lower disk 1202 and an upper disk 1204 thatare connected to one another by multiple, circumferentially spacedcolumns 1206. Each of the columns 1206 includes a weakened region (e.g.,an annular depression or slot) 1208 that facilitates outward bowing ofthe columns 1206 when a downward axial force is applied to the upperdisk 1204. The upper disk 1204 includes a central aperture 1210, whichis sized to receive the spike 136, 736 when the downward axial force isapplied to the upper disk 1204 causing the cylinder 1206 to bend suchthat the upper disk moves 1204 toward the lower disk 1202. The lowerdisk 1202 also includes a central aperture 1212 through which the spike136, 736 extends. The central aperture 1212 in the lower disk 1202 issmaller than the aperture 1210 in the upper disk 1204 so that the lowerdisk 1202 engages the spike 136, 736 and helps to fix the lower disk1202 relative to the spike 136, 736.

Still referring to FIG. 24, pointed projections 1244 (similar to thepointed projections 1044 described with respect to FIG. 21) extend fromthe upper surface of the upper disk 1204. The support columns 1206 areconstructed to provide sufficient axial rigidity (prior to bending) suchthat when the user presses the vial 116, 118 down onto the upper disk1204, the projections 1244 deform the cap 119 of the vial 116, 118,causing discrete deformed regions of the cap 119 penetrate the rubberseal 123 of the vial 116, 118. After the projections 1244 penetrate therubber seal 123, further axial force applied to the upper disk 1202causes the support columns 1206 to bend outward so that the upper disk1204 moves downward toward the lower disk 1202, allowing the spike 136,736 to pierce the rubber seal 123 of the vial 116, 118. The penetrationof the projections 1244 into the rubber seal 123 of the vial 116, 118limits transverse movement of the rubber seal 123 relative to the cap119 as the spike 136, 736 pierces the rubber seal 123. As a result, thedistance by which the central portion of the rubber seal 123 is deformedinto the vial 116, 118 is reduced or minimized. After removing the vial116, 118 from the spike 136, 736, the columns 1206 return to theiroriginal shape such that the cover 1200 again protects the spike 136,736. This can, for example, help to prevent a user from pricking himselfor herself with the spike 136, 736 when disposing the fluid set orcassette of which the spike 136, 736 and cover 1200 are components.

The lower disk 1202, upper disk 1204, and support columns 1206 aretypically formed of a relatively rigid medical grade plastic such asABS. However, other materials that permit the cover 1200 to operate inthe manner described above can alternatively or additionally be used toform those components of the cover 1200.

The lower disk 1202 can be permanently or releasably attached to thespike 136, 736. Any of various techniques can be used to attach thelower disk 1202 to the spike 136, 736. For example, the lower disk 1202can be thermally bonded, chemically bonded, and/or adhesively bonded tothe spike 136, 736. Alternatively, the lower disk 1202 can bemechanically attached (e.g., by a press-fit or interference fit) to thespike 136, 736. Any of the above-noted techniques can similarly be usedto attach the support columns 1206 to the lower and upper disks 1202,1204.

While the cover 1200 has been described as including the support columns1206 with weakened annular regions 1208, other structures that permit acontrolled collapse and subsequent expansion of the cover canalternatively or additionally be used. As shown in FIG. 25, for example,a spike cover 1300 includes a foam sleeve 1306 that is positionedbetween the lower and upper disks 1202, 1204 to permit the upper disk1204 to move toward the lower disk 1202 as the user presses the vial116, 118 downward on the upper disk 1204. In certain implementations,the sleeve 1306 is formed of polyurethane. However, other materials thatprovide the sleeve 1306 with the ability to collapse after a certainforce (e.g., about 1 pound to about 20 pounds, about 1 pound to about 10pounds, about 1 pound to about 5 pounds, about 5 pounds to about 10pounds) is applied to it can be used. Examples of such materials includesilicon, polyethylene, polypropylene, polyethylene/EVA block-type,polyolefin, polyether urethane, and polyester foams.

Referring now to FIG. 26, another spike cover 1400 includes a spiralspring 1406 that is disposed between the lower and upper disks 1202,1204. In some implementations, the spring 1406 is formed ofpolycarbonate. However, the spring 1406 can alternatively oradditionally be formed of other materials, such as ABS, polysulfone,polyethylene, and/or polypropylene.

In some implementations, the lower and upper disks 1202, 1204 are notsecured to one another via an intermediate member. As shown in FIG. 27,for example, a cover 1500 includes a tube 1506 that extends downwardfrom the upper disk 1204. The tube 1506 has an inner diameter that isslightly smaller (e.g., about 0.05 mm to about 0.2 mm smaller) than theouter diameter of the spike 136, 736. The tube 1506 is typically formedof one or more polymeric materials, such as polyurethane, low densitypolyethylene, polyethylene, and/or polypropylene. As the user pressesthe vial 116, 118 down on the upper disk 1204, the larger diameterportion of the spike 136, 736 resists downward movement of the tube 1506and the upper disk 1204 attached thereto. This initial pressure causesthe projections 1244 of the upper disk 1204 to penetrate the rubber seal123 of the vial 116, 118. The application of additional force to thevial 116, 118 then causes the tube 1506 to deform in a manner such thatthe inner diameter of the tube 1506 increases to a size greater than orequal to the outer diameter of the spike 136, 736 and allows the tube1506 and upper disk 1204 to slide downward along the spike 136, 736. Thelength of the tube 1506 is about 20 percent the length of the spike 136,736 to allow the spike to pass through the central aperture 1210 of theupper disk 1204 and pierce the rubber seal 123 of the vial 116, 118 asthe upper disk 1204 and tube 1506 are forced downward along the spike136, 736.

While the upper disk 1204 of the above covers has been described ashaving pointed projections 1244 that penetrate the rubber seal 123 ofthe vial 116, 118 as the vial is pressed down against the upper disk1204, the upper disk 1204 can alternatively be provided with no suchprojections. It has been found that, in certain cases, the applicationof an axial force to the cap 119 of the vial 116, 118 using asubstantially flat surface, such as that of an upper disk including nopointed projections, can sufficiently compress the rubber seal 123between the cap 119 and neck 121 of the vial 116, 118 to resist (e.g.,prevent) transverse movement of the rubber seal 123 relative to the cap119 and neck 121 of the vial 116, 118.

In some implementations, the spike covers include no upper disk. Asshown in FIG. 28, for example, a cover 1600 includes only the spring1406 secured to the lower disk 1202. The length of the spring 1406 in arelaxed (i.e., uncompressed) state is greater than the length of thespike 136, 736. Thus, prior to being compressed by the vial 116, 118,the spring 1406 extends along the entire length of the spike 136, 736 toprevent objects from inadvertently contacting the spike 136, 736 beforethe spike is inserted into the vial 116, 118. As a downward forcesufficient to overcome the resistant force of the spring 1406 is appliedby the vial 116, 118 to the spring 1406, the spring 1406 is compressedand the spike 136, 736 pierces the rubber seal 123 of the vial 116, 118.

Referring to FIG. 29, another cover 1700 includes an inflated orexpanded balloon 1706 that is attached to the lower disk 1202 andsurrounds the spike 136, 736. The balloon 1706 can be formed of one ormore polymeric materials, such as PET, polyurethane, and/or ABS. Tocause the spike 136, 736 to pierce the rubber seal 123 of the vial 116,118, the user presses the vial 116, 118 down against the top of theballoon 1706 with sufficient force to compress the gas within theballoon 1706 and cause the balloon 1706 to move downward into contactwith the tip of the spike 136, 736. The downward movement of the balloon1706 causes the spike 136, 736 to pierce and thus deflate the balloon1706.

While the spike covers described above with respect to FIGS. 24-29 areillustrated in use with spikes 136, 736, which have sharp, tapered tips,the spike covers can used with spikes of different shapes, such as thespikes 236, 336 that are described above with respect to FIGS. 10 and11. These spike covers can be used with any of the drug vial holders ordrug vial spikes described herein.

While some of the of the drug vial spiking devices, drug vial holders,and drug vial spike covers described above include projections that,during use, dent the cap 119 of the drug vial 116, 118 into the rubberseal 123 of the drug vial 116, 118, those projections can alternativelypierce the cap 119 and extend into the rubber seal 123. The projectionscan, for example, be formed with sharper tips such that when the vials116, 118 are pressed against the projections using the methods describedabove, the projections pierce the caps 119. Alternatively oradditionally, the vials 116, 118 can be pressed with greater forceagainst the projections to ensure that the projections pierce the caps119. As a result of the projections piercing the drug vial cap 119,sharp edges of the cap 119 surrounding the holes formed by theprojections will protrude into and grip the rubber seal 123 of the drugvial 116, 118.

In addition, while some of the above-described drug vial spikingdevices, drug vial holders, and drug vial spike covers have beendescribed as including three circumferentially spaced projections thatcan be used to dent or pierce the caps 119 of the drug vials 116, 118,more or fewer than three projections can be used. In certainimplementations, for example, the drug vial spiking devices, drug vialholders, and/or drug vial spike covers are provided with eightprojections that are circumferentially spaced from one another by about45 degrees.

While certain drug delivery devices described herein are provided ascomponents of hemodialysis systems, the drug delivery devices can beused in any type of medical device that would benefit from drug infusioncapabilities. Alternatively, the drug delivery devices described hereincan be configured to be operated as stand alone machines (i.e., notconnected to another medical device). FIG. 30 illustrates a stand alonedrug delivery device 602, which is substantially the same as the drugdelivery device 103 described above but sits on a wheeled cart 660. Thedrug delivery line 104 of this stand alone drug delivery device 602 isconnected to a drip chamber 662. During use, the drug(s) is/aredelivered from the vials 116, 118 to the drip chamber 662. The drug(s)is/are then delivered from the drip chamber 662 to the patient via afluid line 664. The drip chamber 662, similar to the above-describeddrip chamber 106, helps to ensure that any air pulled into the systemfrom the vials does not reach the patient. The drug delivery device 602can be used in a manner similar to the drug delivery device 103described above to deliver drugs to a patient.

While the drug administration fluid line sets have generally beendescribed as including a feeder line 122 and spike 136, 236, 336, 736for each vial location provided in the drug vial holders, the drugadministration fluid line sets can include any of various differentnumbers of feeder lines and spikes. Drug administration fluid line setscan, for example, be manufactured to include one, two, three, or fourfeeder lines and spikes, depending on the number of vials needed fortreatment. As explained above, in certain cases, a treatment may notrequire three Epogen® vials and/or the treatment may not require aVenofer® vial. For those cases, drug administration fluid line setsincluding fewer feeder lines and drug vial spikes can be used.

While certain implementations above involve determining the volume ofdrug delivered by monitoring operation of the drug pump, othertechniques can be used. In some implementations, for example, each ofthe vials is associated with a load scale that weighs the vialthroughout the drug delivery. The change in weight of the vial duringthe drug delivery process can be used to determine the amount of drugdelivered. In certain implementations, a drip counter is provided on thedrip chamber to measure how many drips are delivered. Typically, eachdrop is about 0.05 ml. Thus, the total number of drops can be used todetermine the total volume of drug delivered.

While the drug pumps 132, 732 have been described as peristaltic pumps,other types of mechanical pumps, including but not limited to “finger”peristaltic pumps, diaphragm pumps, solenoid pumps, syringe pumps,hydraulic pumps, piston pumps, pod pumps, and electric motor pumps, canbe used.

While the drug delivery devices described above are equipped with drugvial holders capable of holding up to four vials, the drug deliverydevices can alternatively be equipped with drug vial holders that areconfigured to hold fewer than or greater than four drug vials.Similarly, the drug administration fluid line sets/cassettes to be usedwith those drug vial holders can include fewer than or greater than fourspikes and feeder lines.

While certain drug delivery devices described above include a vialholder configured to hold one vial and another vial holder configured tohold three vials, the drug delivery devices can be provided with anydesired number of vial holders depending on the number of vials desiredto be used during the particular type or types of treatment for whichthe drug delivery devices are designed. In certain implementations, thedrug delivery device includes four separate vial holders, each with itsown drive mechanism. This can permit four vials of different shapes andsizes to be used at the same time.

FIG. 31 illustrates a portion of a hemodialysis machine that includes amodular drug delivery device 502 configured to retain only a singlevial. FIGS. 32 and 33 illustrate the drug delivery device 502 detachedform the hemodialysis machine, and FIG. 34 illustrates an exploded viewof the drug delivery device 502 and its associated drug administrationfluid line set. The drug delivery device 502 is substantially the sameas the drug delivery device 103 described above. However, the drugdelivery device 502 illustrated in FIG. 31 includes a drug vial holderthat includes only one channel 514 instead of four. In addition, thedrug administration fluid line set 107 that is used with the drugdelivery device 520 includes a single drug delivery line 504 that isconnected to the vial 118 via the drug vial spike 120. The drug deliverydevice 502 can be used where only one drug (e.g., Epogen®) is beingadministered to the patient and the prescribed dosage of that drug canbe achieved with a single vial.

While the drip chamber 106 of the hemodialysis systems described aboveis illustrated as an arterial drip chamber (i.e., connected to thearterial patient line that draws blood into the dialysis machine fromthe patient), the drip chamber can alternatively be positioned as avenous drip chamber (i.e., connected to the venous patient line thatreturns blood from the dialysis machine to the patient). In certainimplementations, the dialysis system includes both an arterial dripchamber and a venous drip chamber. In some implementations, the drugdelivery line 104 of the drug administration fluid line set/cassette isconnected to a venous drip chamber located between the dialyzer 110 andthe patient.

While drug delivery devices have been described above as including theirown control unit, the drug delivery device can alternatively oradditionally be configured to communicate with a control unit of thehemodialysis machine. In certain implementations, for example, thevarious components of the dialysis machine, including the drug deliverydevice components, are controlled by a single control unit of thehemodialysis machine.

While certain drug delivery devices discussed above have been describedas having user interfaces by which the operator can input information,such as prescribed drug dosages, those drug delivery devices canalternatively be provided with no user interface. In suchimplementations, for example, the drug delivery device can be incommunication with a user interface of the hemodialysis machine (e.g.,via a control unit of the drug delivery device or a control unit of thehemodialysis machine) such that the operator can use the user interfaceof the hemodialysis machine to input information, such as prescribeddrug dosages, to the drug delivery device.

While the set up of the drug delivery device (e.g., the selection of thedrug vials, the loading of the drug vials and the drug administrationfluid line set, etc.) has been described as occurring after thehemodialysis treatment has begun, the set up of the drug delivery devicecan alternatively take place before the hemodialysis treatment begins.

While the methods of operating the drug delivery devices described aboveinvolve the user inputting a desired dosage prescription into the drugdelivery device (e.g., typing the prescription into the touch screen ofthe drug delivery device), the prescription can alternatively betransmitted to the drug delivery device electronically. In certainimplementations, for example, the desired prescription can be determinedby a physician of the patient to be treated and the physician can inputthe prescription into a secured database or website. The prescriptioncan then be automatically transmitted from the database to the controlunit of the drug delivery device (e.g., to the control unit of thedialysis machine of which the drug delivery device is a part). Thistechnique can help to prevent prescription input errors by the operatorof the drug delivery device.

While the methods describe above including priming the feeder lines 122by running the pump and sequentially opening and closing the occluders128 or by sequentially running the pumps, in certain cases, otherpriming techniques can be used. In certain implementations, for example,a line connected at one end to a priming solution container is connectedat its opposite end to the connector to which the drug delivery line 104is connected during treatment, and the pump or pumps is/are operated inreverse. This draws the priming solution toward the vials. The pumps canbe run in reverse until the priming solution reaches the tip of thespike and thus forces any air in the lines through the spike and intothe vial or to atmosphere in the case that the vial has not yet beenmounted on the spike.

While the methods described above involve delivering the Venofer® priorto the three vials of Epogen®, the drug vials can be emptied indifferent orders. In some implementations, for example, the Venofer® isdelivered last. As a result, the delivery of the Venofer® through thevarious fluid lines and passages of the drug administration fluid lineset/cassette can help to clear those lines and passages of any residualEpogen® remaining from the prior Epogen® deliveries. This technique canthus help to ensure that all of the Epogen® is delivered to the patient.By delivering the Venofer® last, it can also be assured that an airbubble can be fed through the various lines and passages of the drugadministration fluid line set/cassette between delivery of the Venofer®and the Epogen® from the last Epogen® vial because the last Epogen® vialwill be fully evacuated and thus allow air to be drawn from it. Incontrast, the Venofer® vial is not always fully evacuated, so, when theVenofer® is delivered first, it may be more difficult to form the airbubble in the fluid lines and passages. For example, if the Venofer®vial is not fully evacuated, it may be necessary to remove the Venofer®vial from its spike to allow air to be drawn into the feeder line 122associated with that spike.

While complete or substantially complete evacuation of the drug vial hasbeen described as being achieved through the design of the drug vialspikes and/or the drug vial holders, complete evacuation of the drugfrom the vial can alternatively or additionally be accomplished usingother techniques. In some implementations, for example, the vial isflushed with saline to help ensure complete evacuation of the drug vial.In certain implementations, pulse waves are delivered to the vial toshake loose any droplets adhered to the surface area of the vial and/orspike to help ensure complete evacuation of the vial. Liquid surfacetension may cause droplets to adhere to the vial wall or the vial/sealjunction. Mechanical or ultrasonic vibration tuned to a specificresonance based on the vial/spike combination may dislodge droplets andcause them to be evacuated from the vial. Agitation or mechanicaltapping mechanisms can be employed to further break loose droplets.Alternatively or additionally, a non-toxic or inert surfactant could beapplied to the inners surfaces of the vial and rubber seal to reducesurface tension and minimize droplet formation.

In some implementations, the drug vial spike can be vented. A drug vialspike 420 including a vented central spike 436 is shown in FIG. 35. Thecentral spike 436 includes two channels extending therethrough. One ofthe channels extends from one end of the spike to the other to allowfluid to pass from the vial to a connected fluid line during use. Theother channel is in fluid communication with the atmosphere and isequipped with a vent (e.g., a Gortex membrane) 450. The vent 450 iscapable of allowing air to pass therethrough while preventing liquidfrom passing therethrough. As a result, when the drug vial spike 420 isbeing used such that the central spike 436 is disposed inside a drugvial, air can enter the vial via the vent 450 without allowing the drugto escape from the vial via the vent.

It is sometimes difficult to monitor the flow of the drug during directvial delivery, e.g., to confirm delivery of the drug. Therefore, incertain implementations that utilize the above-described vented drugvial spike 420, drug delivery is determined by taking measurements ofthe air pressure in the vial. As shown in FIG. 36, a pressure transducer452 is connected to the vent 450. As a result, air from the vial is ableto pass across the vent 450 and contact the pressure transducer 452.Thus, the pressure transducer 452 is able to detect the air pressurewithin the vial. The air pressure is proportional to the fluid volume(or air volume) in the vial. Therefore, a detected change in airpressure indicates a change in air volume, and thus a change in the drugvolume within the vial. As a result, measuring the fluid volume changein the vial allows for confirmation of delivery of the drug. In additionpressure in the vial, the temperature in the vial can be measured andconveyed to the control unit. This helps to ensure accurate volumecalculations since pressure varies with temperature.

In some implementations, drug delivery is provided for by forcing airinto the vial via the second channel of the central spike 436, whichforces the drug out of the vial via the first channel of the centralspike 436 and into the patient line. Such an arrangement is illustratedin FIG. 37. As shown, a closed volume pressure reservoir 454 containingair is connected to the vent 450 via a fluid line 456. A valve 458 ispositioned along the fluid line 456 to control the delivery of air tothe vial, and thus control the rate at which the drug is forced out ofthe vial. A pressure transducer 460 is fluidly connected to the pressurereservoir 454. Drug delivery is determined by taking measurements of theair pressure in the pressure reservoir 454 using the pressure transducer460. For example, measuring a drop in air pressure within the pressurereservoir 454 can indicate that the air volume within the vial isincreasing and, therefore, that the drug volume within the vial isdecreasing. It is therefore possible to conclude from a drop in pressureat the pressure transducer 460 that drug is being delivered from thevial.

While the drug vials 116, 118 have been described as including rubberseals, the seals can alternatively or additionally be formed of otherresilient materials that are capable of being pierced by the drug vialspikes described herein. Examples of some such materials includesilicon, rubber, and butyl rubber.

While the seals 123 of the vials 116, 118 have been described as beingheld between the cap 119 and the neck portion 121 of the vial 116, 118,vials of other configurations can be used. In certain implementations,for example, vials that do not include neck portions are used. Thosevials include a body portion of substantial uniform diameter along itslength and a seal held between the body portion and a cap of the vial.

While the drug vials have been described as being used in the drugdelivery systems and methods described above, in certainimplementations, other types of drug containers, such as bags, bottles,etc., are used.

While the drug delivery devices above have been described as being usedto deliver Venofer® and/or Epogen®, it should be understood that theterm “drug” as used herein incorporates pharmaceuticals as well as otherfluids delivered to a patient intravenously. Other drugs that arecontemplated to be automatically delivered to the patient in accordancewith the various implementations of the invention, include but are notlimited to, phosphate binders, vitamin D, and anticoagulants.

Other implementations are within the scope of the following claims.

1. A drug delivery device, comprising: a drug vial holder comprising anupper member and a lower member, the upper and lower members beingconfigured to receive a drug vial therebetween; and a mechanismconfigured to move at least one of the upper and lower members relativeto the other of the upper and lower members such that, when a drug vialis disposed between the upper and lower members and the at least one ofthe upper and lower members is moved toward the other, the drug vial iscompressed between the upper and lower members.
 2. The drug deliverydevice of claim 1, wherein the mechanism is configured to compress aseal disposed between a cap of the drug vial and a neck portion of thedrug vial when the drug vial is disposed between the upper and lowermembers and the at least one of the upper and lower members is movedtoward the other.
 3. The drug delivery device of claim 1, wherein aplurality of projections extend from a surface of the lower member, theprojections being configured to dent adjacent portions of a cap of thedrug vial into a seal of the drug vial when the drug vial is compressedbetween the upper and lower members.
 4. The drug delivery device ofclaim 3, wherein the projections are configured to pierce the adjacentportions of the cap of the drug vial when the drug vial is compressedbetween the upper and lower members.
 5. The drug delivery device ofclaim 1, wherein the lower member defines an opening sized to receive adrug vial spike, and the opening is arranged to align with a seal of thedrug vial when the drug vial is disposed between the upper and lowermembers.
 6. The drug delivery device of claim 1, wherein the lowermember defines a recess configured to receive a portion of the drug vialtherein.
 7. The drug delivery device of claim 1, wherein the mechanismis configured to move the upper member, the lower member, and the drugvial disposed therebetween in unison after compressing the drug vialbetween the upper and lower members.
 8. The drug delivery device ofclaim 1, wherein the mechanism comprises a motor that, when operated,causes the at least one of the upper and lower members to move towardthe other.
 9. The drug delivery device of claim 8, wherein the mechanismis configured in a manner such that, after operating the motor for aperiod of time to compress the drug vial between the upper and lowermembers, continued operation of the motor causes the upper and lowermembers to move in unison.
 10. The drug delivery device of claim 1,wherein the mechanism is configured to move the upper member of the drugvial holder toward the lower member of the drug vial holder.
 11. Thedrug delivery device of claim 1, wherein the mechanism comprises arotatable, threaded drive shaft to which a threaded drive member issecured, and the drive member is configured such that rotation of thedrive shaft causes the drive member to move axially along the driveshaft.
 12. The drug delivery device of claim 11, wherein the drivemember comprises a ball screw.
 13. The drug delivery device of claim 11,wherein the drive member is secured to the upper member of the vialholder in a manner such that axial movement of the drive member causesaxial movement of the upper member.
 14. The drug delivery device ofclaim 13, wherein the drive member is secured to a cross bar that isattached to at least one extension member, and the at least oneextension member is attached to the upper member of the drug vialholder.
 15. The drug delivery device of claim 1, wherein the mechanismcomprises at least one resilient member configured to resist downwardmovement of the lower member of the drug vial holder.
 16. The drugdelivery device of claim 15, wherein the at least one resilient membercomprises a spring.
 17. The drug delivery device of claim 15, whereinthe at least one resilient member is configured to provide sufficientresistance to downward movement of the lower member to cause a seal of adrug vial disposed between the upper and lower members to be compressedwhen the at least one of the upper and lower members is moved toward theother.
 18. The drug delivery device of claim 17, wherein the at leastone resilient member is configured to collapse and allow the drug vialto move in unison with the upper and lower members after the seal of thedrug vial has been compressed.
 19. The drug delivery device of claim 1,further comprising at least one spike disposed beneath the drug vialholder, wherein the mechanism is configured to move the upper and lowermembers of the drug vial holder in unison relative to the spike to causethe spike to penetrate a drug vial disposed between the upper and lowermembers.
 20. The drug delivery device of claim 1, further comprising apump configured to be operably connected to a fluid line that is influid communication with a drug vial disposed between the upper andlower members of the drug vial holder such that operation of the pumpcan draw drug from the drug vial and through the fluid line.
 21. Thedrug delivery device of claim 1, wherein the mechanism is manuallyoperable.
 22. A drug delivery system, comprising: a drug delivery devicecomprising a drug vial holder comprising an upper member and a lowermember; and a mechanism connected to the drug vial holder; and a drugvial disposed between the upper and lower members of the drug vialholder, wherein the mechanism is configured to move at least one of theupper and lower members relative to the other of the upper and lowermembers in a manner to compress the drug vial therebetween.
 23. The drugdelivery system of claim 22, wherein the mechanism is configured tocompress a seal disposed between a cap of the drug vial and a neckportion of the drug vial when the at least one of the upper and lowermembers is moved toward the other.
 24. The drug delivery system of claim22, wherein a plurality of projections extend from a surface of thelower member, the projections being configured to dent adjacent portionsof a cap of the drug vial into a seal of the drug vial when the drugvial is compressed between the upper and lower members.
 25. The drugdelivery system of claim 22, wherein the mechanism is configured to movethe upper member, the lower member, and the drug vial disposedtherebetween in unison after compressing the drug vial between the upperand lower members.
 26. The drug delivery system of claim 22, wherein themechanism is configured to move the upper member of the drug vial holdertoward the lower member of the drug vial holder.
 27. The drug deliverysystem of claim 22, further comprising a spike disposed beneath the drugvial holder, wherein the mechanism is configured to move the upper andlower members of the drug vial holder in unison relative to the spike tocause the spike to penetrate a drug vial disposed between the upper andlower members.
 28. The drug delivery system of claim 22, furthercomprising a pump configured to be operably connected to a fluid linethat is in fluid communication with the drug vial disposed between theupper and lower members of the drug vial holder such that operation ofthe pump can draw drug from the drug vial and through the fluid line.29. A dialysis system, comprising: a dialysis machine comprising a bloodpump; a drug delivery device comprising a drug pump; a drug vial holdercomprising an upper member and a lower member; and a mechanismconfigured to move at least one of the upper and lower members relativeto the other of the upper and lower members such that, when a drug vialis disposed between the upper and lower members and the at least one ofthe upper and lower members is moved toward the other, the drug vial iscompressed between the upper and lower members; a blood line setcomprising a blood line that is operably connected to the blood pump;and a fluid line set comprising a fluid line that is operably connectedto the drug pump and is connected to a spike, the fluid line set beingconfigured such that the spike can be placed in fluid communication withthe drug vial retained between the upper and lower members of the drugvial holder by moving the drug vial holder and the drug vial relative tothe spike, wherein the fluid line is in fluid communication with theblood line set such that a drug can be delivered from the drug vial tothe blood line set when the drug pump is operated.
 30. A method,comprising: inserting a spike through a seal of a drug vial to allowfluid communication between an interior of the drug vial and a channeldefined by the spike; and deforming a portion of the seal away from abody of the drug vial to facilitate removal of drug from the interior ofthe drug vial, wherein deforming the portion of the seal away from thebody of the drug vial comprises using a mechanism to move the spikerelative to the drug vial.
 31. The method of claim 30, wherein the sealis a rubber seal.
 32. The method of claim 30, wherein deforming theportion of the seal comprises using the spike to apply a force to theportion of the seal.
 33. The method of claim 32, wherein the force is africtional force.
 34. The method of claim 33, wherein moving the spikerelative to the vial comprises applying a force to the body of the drugvial in a direction opposite the force applied to the portion of theseal.
 35. The method of claim 30, further comprising maintaining theseal in a compressed state while inserting the spike through the seal.36. The method of claim 35, wherein the seal is compressed between a capof the drug vial and a neck portion of the drug vial.
 37. The method ofclaim 35, wherein the seal is compressed between a cap of the drug vialand a body portion of the drug vial.
 38. The method of claim 30, whereinthe mechanism comprises a spring.
 39. The method of claim 30, whereinthe mechanism is an automated mechanism.
 40. A method, comprising:compressing a seal of a drug vial between a cap of the drug vial and aneck portion or body portion of the drug vial by disposing the drug vialbetween an upper member and a lower member of a drug vial holder andmoving at least one of the upper and lower members of the drug vialholder toward the other of the upper and lower members of the drug vialholder; and while maintaining the seal in a compressed state, insertinga spike through the seal of the drug vial to allow fluid communicationbetween an interior of the drug vial and a channel defined by the spike.41. The method of claim 40, wherein the seal is compressed between a capof the drug vial and a neck portion of the drug vial.
 42. The method ofclaim 40, wherein the seal is a rubber seal.
 43. The method of claim 40,further comprising denting portions of the cap into the seal.
 44. Themethod of claim 43, wherein denting the portions of the cap into theseal comprises forcing the cap against projections extending from asurface of the lower member of the drug vial holder.
 45. The method ofclaim 43, wherein denting the portions of the cap into the sealcomprises piercing portions of the cap.
 46. The method of claim 40,further comprising deforming a portion of the seal away from a body ofthe drug vial to facilitate removal of drug from the drug vial.
 47. Themethod of claim 46, wherein deforming the portion of the seal comprisesusing the spike to apply a force to the portion of the seal.
 48. Themethod of claim 47, wherein the force is a frictional force.
 49. Themethod of claim 48, further comprising applying a force to the bodyportion of the drug vial in a direction opposite the force applied tothe portion of the seal.
 50. The method of claim 48, further comprisingapplying a force to the neck portion of the drug vial in a directionopposite the force applied to the portion of the seal.